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1
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Parvizi M, Vaezi M, Jeddi F, Bakhshandeh M, Eghdam-Zamiri R, Mobaraki-Asl N, Esmati E, Karimi A. The role and diagnostic value of deregulated miRNAs in cervical cancer. Discov Oncol 2025; 16:922. [PMID: 40413660 DOI: 10.1007/s12672-025-02744-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Accepted: 05/17/2025] [Indexed: 05/27/2025] Open
Abstract
Cervical cancer (CC) remains a significant global health concern, particularly affecting women in low-income countries. Despite advancements in screening programs, CC continues to pose a substantial mortality risk, highlighting the need to explore diagnostic and treatment modalities. This review focuses on the role of deregulated microRNAs (miRNAs) in CC development, emphasizing their potential as biomarkers for early detection and prognosis in body fluids. miRNAs have emerged as critical regulators of key cellular processes, including proliferation, migration, invasion, and apoptosis, and their dysregulation is closely linked to CC progression. Upregulated miRNAs such as miR-146b-3p, miR-1908, and miR-21 promote CC progression by targeting tumor suppressor genes, while downregulated miRNAs like miR-23-3p and miR-4262 are associated with reduced tumor aggressiveness. miRNAs also hold significant promise as non-invasive prognostic biomarkers. Their expression levels correlate with clinical outcomes, including tumor stage, metastasis, and overall survival, making them valuable tools for risk stratification and personalized treatment strategies. Liquid biopsies, which detect circulating miRNAs in bodily fluids, offer a minimally invasive approach to monitor tumor dynamics and predict patient outcomes. Furthermore, exosomal miRNAs are emerging as promising diagnostic and prognostic tools for CC. Advanced diagnostic technologies and bioinformatics tools are anticipated to enhance the identification of evident miRNA biomarkers in the clinical settings. Standardized protocols for sample collection and analysis will improve the reproducibility of miRNA studies, while a deeper understanding of miRNA biology may unlock their potential as therapeutic targets. In conclusion, this review consolidates current research on deregulated miRNAs in CC, highlighting their diagnostic and prognostic significance. The findings underscore the potential of miRNAs to revolutionize CC management through innovative diagnostic and therapeutic strategies.
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Affiliation(s)
- Masoumeh Parvizi
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Vaezi
- Obstetric and Oncology Department, School of Medicine, Women's Reproductive Health Research Center, Clinical Research Institute, Alzahra Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farhad Jeddi
- Department of Genetics and Pathology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Masoumeh Bakhshandeh
- Obstetric and Oncology Department, School of Medicine, Women's Reproductive Health Research Center, Clinical Research Institute, Alzahra Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Eghdam-Zamiri
- Department of Radiation Oncology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Noushin Mobaraki-Asl
- Department of Obstetrics and Gynecology, School of Medicine, Alavi Hospital, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Ebrahim Esmati
- Department of Radiation Oncology, Cancer Institute, IKHC, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Karimi
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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2
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Mukherjee A, Boonbangyang M, K S M. Unraveling the intricate molecular landscape and potential biomarkers in lung adenocarcinoma through integrative epigenomic and transcriptomic profiling. Sci Rep 2025; 15:9154. [PMID: 40097569 PMCID: PMC11914463 DOI: 10.1038/s41598-025-93769-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 03/10/2025] [Indexed: 03/19/2025] Open
Abstract
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortalities, characterized by substantial genetic heterogeneity that challenges a comprehensive understanding of its progression. This study employs next-generation sequencing data analysis to transform our comprehension of LUAD pathogenesis. Integrating epigenetic and transcriptomic data of LUAD patients, this approach assessed the critical regulatory occurrences, identified therapeutic targets, and offered profound insights into cancer molecular foundations. We employed the DNA methylation data to identify differentially methylated CpG sites and explored the transcriptome profiles of their adjacent genes. An intersectional analysis of gene expression profiles uncovered 419 differentially expressed genes (DEGs) influenced by smoke-induced differential DNA methylation, among which hub genes, including mitochondrial ribosomal proteins (MRPs), and ribosomal proteins (RPs) such as MRPS15, MRPS5, MRPL33, RPL24, RPL7L1, MRPL15, TUFM, MRPL22, and RSL1D1, were identified using a network-based approach. These hub genes were overexpressed and enriched to RNA processing, ribosome biogenesis, and mitochondrial translation, which is critical in LUAD progression. Enhancer Linking Methylation/Expression Relationship (ELMER) analysis revealed transcription factor (TF) binding motifs, such as JUN, NKX23, FOSB, RUNX3, and FOSL1, which regulated these hub genes through methylation-dependent enhancer dynamics. Predominant hypomethylation of MRPs and RPs disrupted mitochondrial function, contributed to oxidative phosphorylation (OXPHOS) and metabolic reprogramming, favoring cancer cell survival. The survival analysis validated the clinical relevance of these hub genes, with high-expression cohorts exhibiting poor overall survival (OS) outcomes enlightened their relevance in LUAD pathogenesis and presented the potential for developing novel targeted therapeutic strategies.
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Affiliation(s)
- Arnab Mukherjee
- Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Manipal, India
| | - Manon Boonbangyang
- Pornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Mukunthan K S
- Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Manipal, India.
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3
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Oh JH, Pareja F, Elkin R, Xu K, Norton L, Deasy JO. Biological correlates associated with high-risk breast cancer patients identified using a computational method. NPJ Breast Cancer 2025; 11:8. [PMID: 39875417 PMCID: PMC11775240 DOI: 10.1038/s41523-025-00725-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 01/19/2025] [Indexed: 01/30/2025] Open
Abstract
Using a novel unsupervised method to integrate multi-omic data, we previously identified a breast cancer group with a poor prognosis. In the current study, we characterize the biological features of this subgroup, defined as the high-risk group, using various data sources. Assessment of three published hypoxia signatures showed that the high-risk group exhibited higher hypoxia scores (p < 0.0001 in all three signatures), compared to the low-risk group. Our analysis of the immune cell composition using CIBERSORT and leukocyte fraction showed significant differences between the high and low-risk groups across the entire cohort, as well as within PAM50 subtypes. Within the basal subtype, the low-risk group had a statistically significantly higher spatial fraction of tumor-infiltrating lymphocytes (TILs) compared to the high-risk group (p = 0.0362). Our findings indicate that this subgroup with poor prognosis is driven by a distinct biological signature with high activation of hypoxia-related genes as well as a low number of TILs.
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Affiliation(s)
- Jung Hun Oh
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - Fresia Pareja
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Rena Elkin
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kaiming Xu
- Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA
| | - Larry Norton
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Joseph O Deasy
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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4
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Shanthala S, Amirtham U, Lokesh KN, Jacob L, Babu G. Clinicopathological Evaluation of Patients with Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Progressing on Endocrine Treatment: A Real-World Retrospective Study from a Regional Cancer Center. South Asian J Cancer 2025; 14:15-22. [PMID: 40124154 PMCID: PMC11925626 DOI: 10.1055/s-0043-1775806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/25/2025] Open
Abstract
Metastatic breast cancer (MBC) is an incurable disease with the primary aim of treatment being the improvement of the patient's quality of life and the delay of disease progression. A substantial proportion of patients with hormone receptor (HR)-positive MBC eventually experience progression despite endocrine treatment. As endocrine resistance remains a significant challenge, we aim to comprehend the intricate relationship between clinicopathological characteristics and the utility of various parameters as predictive markers for hormonal treatment response. This study, conducted at a single center, is ambispective in nature and includes hormone receptor (HR)-positive, human epidermal growth factor 2-negative MBC patients who progressed while on endocrine treatment, selected through purposeful sampling. Nominal data were analyzed in terms of frequency distribution, and continuous variables were represented as median/mean ± standard deviation. Spearman's correlation test and chi-square test were employed to examine variable dependencies. Data comparisons were performed using the independent t-test, one-way analysis of variance, or Mann-Whitney's test. The majority of our study participants ( n = 44, 64.70%) presented with de novo metastasis, while the remainder ( n = 24, 35.29%) were patients who progressed from early-stage breast cancer to metastasis. The overall mean age of our study population at presentation was 47 ± 11 years. Patients with upfront stage 4 tumors presented at an older age, exhibited grade 2 tumors, had a higher frequency of bone-only metastasis, and experienced longer progression-free survival (PFS) compared to patients who progressed from the early stage to metastasis. Multiple visceral involvements had a significant negative impact on PFS in contrast to cases with single visceral or bone-only involvement. No significant associations with PFS were observed for the Ki-67 index, first-line chemotherapy, or endocrine therapy. The extent of metastasis to various organs emerged as the most influential factor in determining PFS. Consequently, we propose the necessity for larger prospective studies aimed at identifying superior or additional biomarkers.
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Affiliation(s)
- S. Shanthala
- Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
| | - Usha Amirtham
- Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
| | - K. N. Lokesh
- Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
| | - Linu Jacob
- Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
| | - Govinda Babu
- Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
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Pleșea RM, Riza AL, Ahmet AM, Gavrilă I, Mituț A, Camen GC, Lungulescu CV, Dorobanțu Ș, Barbu A, Grigorescu A, Mirea CS, Schenker M, Burada F, Streață I. Clinically Significant BRCA1 and BRCA2 Germline Variants in Breast Cancer-A Single-Center Experience. Cancers (Basel) 2024; 17:39. [PMID: 39796670 PMCID: PMC11718772 DOI: 10.3390/cancers17010039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/17/2024] [Accepted: 12/23/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND Conditions associated with BRCA1/2 pathogenic (PVs) or likely pathogenic variants (LPVs) are often severe. The early detection of carrier status is ideal, as it provides options for effective case management. MATERIALS AND METHODS The study involved 58 patients with a personal and familial history of breast cancer (BC) who underwent genetic testing at the Regional Centre for Medical Genetics Dolj over a three-year period. An immunohistochemical panel (HER2, ER, PR, and Ki-67) was used to define the molecular subtypes of breast tumors. The AmpliSeq for Illumina BRCA Panel was used to evaluate germline variants in the BRCA1 and BRCA2 genes in patients with BC. The χ2 test and Fisher's exact test were used to compare the different parameters studied. RESULTS Our findings revealed that 15.5% of the patients carried either BRCA1 or BRCA2 PVs or LPVs. BRCA1 carriers had aggressive tumors whereas BRCA2 carriers had rather low-grade tumors. CONCLUSIONS The study revealed that PVs in both BRCA genes have a significant frequency among BC patients in our region, and BRCA1 carriers tend to develop more aggressive tumors than carriers of BRCA2 PVs and patients with no germline PVs in either of the two genes. These observations could provide new epidemiologic data for this disease in our region and contribute further to the development of national screening strategies.
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Affiliation(s)
- Răzvan Mihail Pleșea
- Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania; (R.M.P.); (A.-L.R.); (A.M.); (Ș.D.); (A.B.); (F.B.); (I.S.)
- Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania;
| | - Anca-Lelia Riza
- Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania; (R.M.P.); (A.-L.R.); (A.M.); (Ș.D.); (A.B.); (F.B.); (I.S.)
- Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania;
| | - Ana Maria Ahmet
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Ionuț Gavrilă
- Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania; (R.M.P.); (A.-L.R.); (A.M.); (Ș.D.); (A.B.); (F.B.); (I.S.)
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Andreea Mituț
- Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania; (R.M.P.); (A.-L.R.); (A.M.); (Ș.D.); (A.B.); (F.B.); (I.S.)
| | - Georgiana-Cristiana Camen
- Department of Radiology and Medical Imaging, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Cristian Virgil Lungulescu
- Department of Medical Oncology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Ștefania Dorobanțu
- Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania; (R.M.P.); (A.-L.R.); (A.M.); (Ș.D.); (A.B.); (F.B.); (I.S.)
- Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania;
| | - Adina Barbu
- Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania; (R.M.P.); (A.-L.R.); (A.M.); (Ș.D.); (A.B.); (F.B.); (I.S.)
- Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania;
| | - Andra Grigorescu
- Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania;
| | - Cecil Sorin Mirea
- Department of Surgical Semiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Michael Schenker
- Department of Medical Oncology, Sfantul Nectarie Oncology Center, 200801 Dolj, Romania;
| | - Florin Burada
- Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania; (R.M.P.); (A.-L.R.); (A.M.); (Ș.D.); (A.B.); (F.B.); (I.S.)
- Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania;
| | - Ioana Streață
- Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania; (R.M.P.); (A.-L.R.); (A.M.); (Ș.D.); (A.B.); (F.B.); (I.S.)
- Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania;
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6
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Jeong SJ, Oh JH, Cho JY. ALYREF enhances breast cancer progression by regulating EZH2. Heliyon 2024; 10:e37749. [PMID: 39386827 PMCID: PMC11462240 DOI: 10.1016/j.heliyon.2024.e37749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 08/08/2024] [Accepted: 09/09/2024] [Indexed: 10/12/2024] Open
Abstract
Breast cancer is one of the most common malignant tumors in women worldwide. Similarly, Canine mammary tumors (CMTs) are mostly diagnosed as spontaneous diseases in female dogs. Many studies have suggested that CMTs serve as good models for human breast cancer. However, comparative approaches to histone modifications are still lacking. This study aimed to compare the canine mammary tumor Histone H3 lysine 4 trimethylation (H3K4me3) landscape with that in human breast cancer. Our H3K4me3 ChIP-seq data from CMTs revealed a significant enrichment of H3K4me3 in the ALYREF gene promoter in tumor tissues compared to normal tissues. Furthermore, our study and publicly available RNA-sequencing data revealed that ALYREF expression was elevated in malignant tissues and breast cancer cell lines, and its upregulation was associated with poor prognosis in humans. Depletion of ALYREF resulted in changes in cellular phenotypes, including increased proliferation and colony formation, as well as decreased apoptosis. ALYREF increased cell viability and anchorage-independent growth while decreasing apoptosis by regulating the mRNA expression and protein levels of enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), which promotes hormone receptor-positive breast cancer and CMTs via epigenetic modifications. This suggests that ALYREF may function as a contributing factor to malignant transformation in both CMT and human breast cancer.
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Affiliation(s)
- Su-Jin Jeong
- Department of Biochemistry, College of Veterinary Medicine, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, Republic of Korea
- Comparative Medicine Disease Research Center, Seoul National University, Seoul, 08826, Republic of Korea
| | - Ji Hoon Oh
- Department of Biochemistry, College of Veterinary Medicine, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, Republic of Korea
- Comparative Medicine Disease Research Center, Seoul National University, Seoul, 08826, Republic of Korea
| | - Je-Yoel Cho
- Department of Biochemistry, College of Veterinary Medicine, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, Republic of Korea
- Comparative Medicine Disease Research Center, Seoul National University, Seoul, 08826, Republic of Korea
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7
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Mukherjee A, Yadav PH, Mukunthan KS. Unveiling Potential Targeted Therapeutic Opportunities for Co-Overexpressed Targeting Protein for Xklp2 and Aurora-A Kinase in Lung Adenocarcinoma. Mol Biotechnol 2024; 66:2792-2803. [PMID: 37768502 PMCID: PMC11467107 DOI: 10.1007/s12033-023-00879-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 08/30/2023] [Indexed: 09/29/2023]
Abstract
Lung adenocarcinoma (LUAD) is one of the most prevalent and leading causes of cancer deaths globally, with limited diagnostic and clinically significant therapeutic targets. Identifying the genes and processes involved in developing and progressing LUAD is crucial for developing effective targeted therapeutics and improving patient outcomes. Therefore, the study aimed to explore the RNA sequencing data of LUAD from The Cancer Genome Atlas (TCGA) and gene expression profile datasets involving GSE10072, GSE31210, and GSE32863 from the Gene Expression Omnibus (GEO) databases. The differential gene expression and the downstream analysis determined clinically significant biomarkers using a network-based approach. These therapeutic targets predominantly enriched the dysregulation of mitotic cell cycle regulation and revealed the co-overexpression of Aurora-A Kinase (AURKA) and Targeting Protein for Xklp2 (TPX2) with high survival risk in LUAD patients. The hydrophobic residues of the AURKA-TPX2 interaction were considered as the target site to block the autophosphorylation of AURKA during the mitotic cell cycle. The tyrosine kinase inhibitor (TKI) dacomitinib demonstrated the strong binding potential to hinder TPX2, shielding the AURKA destabilization. This in silico study lays the foundation for repurposing targeted therapeutic options to impede the Protein-Protein Interactions (PPIs) in LUAD progression and aid in future translational investigations.
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Affiliation(s)
- Arnab Mukherjee
- Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | | | - K S Mukunthan
- Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
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8
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He Y, Duan S, Wang W, Yang H, Pan S, Cheng W, Xia L, Qi X. Integrative radiomics clustering analysis to decipher breast cancer heterogeneity and prognostic indicators through multiparametric MRI. NPJ Breast Cancer 2024; 10:72. [PMID: 39112498 PMCID: PMC11306571 DOI: 10.1038/s41523-024-00678-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 07/19/2024] [Indexed: 08/10/2024] Open
Abstract
Breast cancer diagnosis and treatment have been revolutionized by multiparametric Magnetic Resonance Imaging (mpMRI), encompassing T2-weighted imaging (T2WI), Diffusion-weighted imaging (DWI), and Dynamic Contrast-Enhanced MRI (DCE-MRI). We conducted a retrospective analysis of mpMRI data from 194 breast cancer patients (September 2019 to October 2023). Using 'pyradiomics' for radiomics feature extraction and MOVICS for unsupervised clustering. Interestingly, we identified two distinct patient clusters associated with significant differences in molecular subtypes, particularly in Luminal A subtype distribution (p = 0.03), estrogen receptor (ER) (p = 0.01), progesterone receptor (PR) (p = 0.04), mean tumor size (p < 0.01), lymph node metastasis (LNM) (p = 0.01), and edema (p < 0.01). Our study emphasizes mpMRI's potential in breast cancer by using radiomics-based cluster analysis to categorize tumors, uncovering heterogeneity, and aiding in personalized treatment strategies.
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Affiliation(s)
- Yongsheng He
- Department of Radiology, Ma'anshan People's Hospital, Ma'anshan, Anhui, 243000, China
| | - Shaofeng Duan
- Department of Radiology, Ma'anshan People's Hospital, Ma'anshan, Anhui, 243000, China
| | - Wuling Wang
- Department of Radiology, Ma'anshan People's Hospital, Ma'anshan, Anhui, 243000, China
| | - Hongkai Yang
- Department of Radiology, Ma'anshan People's Hospital, Ma'anshan, Anhui, 243000, China
| | - Shuya Pan
- Department of Radiology, Ma'anshan People's Hospital, Ma'anshan, Anhui, 243000, China
| | - Weiqun Cheng
- Ma'anshan Clinical College, Anhui Medical University, Hefei, Anhui, 230032, China
| | - Liang Xia
- Department of Radiology, Sir Run Run Hospital affiliated to Nanjing Medical University, Nanjing, Jiangsu, 211000, China
| | - Xuan Qi
- Department of Radiology, Ma'anshan People's Hospital, Ma'anshan, Anhui, 243000, China.
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9
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Haryana SM, Ardiansyah SA, Noficandra H, Wardana T, Sesotyosari SL, Afira FR, Satriyo PB, Setiasari DW, Heriyanto DS. G2/M Checkpoint Modulation: Insights from miRNA Profiles in FAM and Breast Cancer. Asian Pac J Cancer Prev 2024; 25:2661-2668. [PMID: 39205563 PMCID: PMC11495450 DOI: 10.31557/apjcp.2024.25.8.2661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Indexed: 09/04/2024] Open
Abstract
OBJECTIVE The aim of this research is to understand the role of microRNA in cell cycle regulation especially on G2M Checkpoint from Luminal A samples Indonesian population. The profile results are used as biomarkers and therapeutic targets for breast cancer. For this reason, analysis was carried out on the comparison of miRNA expression between Luminal A and Fibroadenoma mamae (FAM) using Nanostring nCounter. METHODS In this study, 5 (Formalin-Fixed Paraffin-Embedded) FFPE Luminal A tissues and 4 FFPE FAM samples were used. RNA was isolated from cancer tissue samples. Differential expression analysis of miRNA was conducted using Nanostring nCounter technology, subsequently followed by the expression analysis between FAM and Luminal A using nSolver softwere. Elevated expression levels of miRNAs were subjected to pathway and gene regulation analysis using KEGG and GSEA MsigDB databases. Data visualization was performed utilizing Cytoscape, NetworkAnalyst, and SRplot tools. RESULT Based on 792 miRNAs detected on Nanostring nCounter, it was found that 60 miRNAs were upregulated and 6 miRNAs were downregulated. The 15 upregulated miRNAs analyzed show their role in the G2M Checkpoint through several pathways. The five miRNAs that significantly regulate the G2M Checkpoint are hsa-miR-196b-5p, hsa-miR-218-5p, hsa-miR-7-5p, hsa-miR-19a-5p, and hsa-miR-18a-5p Where each of these miRNAs regulates the CDKN1B gene. CONCLUSION Significant differences in the expression of multiple miRNAs between Luminal A and FAM samples were observed. Furthermore, several of these miRNAs were found to modulate the G2M Checkpoint in Luminal A cancer by suppressing tumor suppressor genes.
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Affiliation(s)
- Sofia Mubarika Haryana
- Study Program of Biotechnology, Graduate School, Universitas Gadjah Mada, Yogyakarta, Indonesia.
| | - Syamsul Arif Ardiansyah
- Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
| | - Habibullah Noficandra
- Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
| | - Tirta Wardana
- Department Biomedicine, School of Dentistry, Faculty of Medicine Jenderal Soedirman University, Jawa Tengah, Indonesia.
| | | | - Fathiya Rahma Afira
- Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
| | - Pamungkas Bagus Satriyo
- Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
| | - Dicka Wahyu Setiasari
- Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
| | - Didik Setyo Heriyanto
- Study Program of Biotechnology, Graduate School, Universitas Gadjah Mada, Yogyakarta, Indonesia.
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10
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Oey O, Wijaya W, Redfern A. Eribulin in breast cancer: Current insights and therapeutic perspectives. World J Exp Med 2024; 14:92558. [PMID: 38948420 PMCID: PMC11212747 DOI: 10.5493/wjem.v14.i2.92558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 02/21/2024] [Accepted: 03/20/2024] [Indexed: 06/19/2024] Open
Abstract
Eribulin is a non-taxane synthetic analogue approved in many countries as third-line treatment for the treatment of patients with metastatic breast cancer. In addition to its mitotic property, eribulin has non-mitotic properties including but not limited to, its ability to induce phenotypic reversal of epithelial to mesenchymal transition, vascular remodelling, reduction in immunosuppressive tumour microenvironment. Since approval, there has been a surge in studies investigating the application of eribulin as an earlier-line treatment and also in combination with other agents such as immunotherapy and targeted therapy across all breast cancer sub-types, including hormone receptor positive, HER2 positive and triple negative breast cancer, many demonstrating promising activity. This review will focus on the application of eribulin in the treatment of metastatic breast cancer across all subtypes including its role as an earlier-line agent, its toxicity profile, and potential future directions.
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Affiliation(s)
- Oliver Oey
- Faculty of Medicine, University of Western Australia, Nedlands 6009, Australia
- Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands 6009, WA, Australia
| | - Wynne Wijaya
- Department of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom
- Department of Internal Medicine, Universitas Gadjah Mada, Sleman 55281, Indonesia
| | - Andrew Redfern
- Department of Medical Oncology, Fiona Stanley Hospital, Murdoch 6150, WA, Australia
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11
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West MA, Rahman S, Jack S, Grocott MP, Levett DZ, the Perioperative Exercise Testing and Training Society (POETTS), Rashid Y, Griffiths J, Ezra M, Ayres L, Neville-Webbe H, Javed MS, Shrotri M, Khan I, Whitmore D, Prabhu P, Timbrell D, Allen S, Packham AO, Sharpe D, Anderson H, Minto G, McAleer S, McPhail S, Alasmar M, Hartley RA, Sultan J, Grace B, Underwood TJ, Byrne J, Noble F, Kelly J, Ansell G, Edwards M. Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study. BJA OPEN 2024; 10:100289. [PMID: 38947220 PMCID: PMC11214286 DOI: 10.1016/j.bjao.2024.100289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 05/01/2024] [Indexed: 07/02/2024]
Abstract
Background Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration NCT03637647.
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Affiliation(s)
- Malcolm A. West
- School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
| | - Saqib Rahman
- School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Sandy Jack
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Michael P.W. Grocott
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Denny Z.H. Levett
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - the Perioperative Exercise Testing and Training Society (POETTS)
- School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
- Departments of Anaesthesia and Critical Care, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
- Department of General Surgery, Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
- Countess of Chester Hospital NHS Foundation Trust, Chester, UK
- Department of Anaesthetics, The Royal Surrey Foundation NHS Trust, Guildford, UK
- Anaesthetic Department, Frimley Park Hospital, Frimley Health NHS Foundation Trust, UK
- Department of General Surgery, The Royal Surrey NHS Foundation Trust Hospital, Minimal Access Therapy Training Unit (MATTU), Guildford, UK
- Department of Anaesthesia, University Hospitals of Leicester NHS Trust, Leicester, UK
- Department of Gastro-Intestinal Surgery, University Hospitals of Leicester NHS Trust, Leicester, UK
- Directorate of Anaesthesia, University Hospitals Plymouth NHS Trust, Plymouth, UK
- Emergency Medical Retrieval and Transfer Service, Cymru, Joint Hospital Group (Southwest), UK
- Institute of Naval Medicine, Alverstoke, UK
- Salford Royal NHS Foundation Trust, Salford Royal, Salford, UK
- Division of Cancer Sciences, School of Medical Sciences, University of Manchester, UK
- University Hospitals Southampton, Department of Surgery, Southampton, UK
| | - Yasir Rashid
- Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - John Griffiths
- Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - Martin Ezra
- Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - Lyndsay Ayres
- Departments of Anaesthesia and Critical Care, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Helen Neville-Webbe
- Departments of Anaesthesia and Critical Care, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
- Department of General Surgery, Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Muhammad Shafiq Javed
- Department of General Surgery, Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Milind Shrotri
- Department of General Surgery, Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Iftikhar Khan
- Department of General Surgery, Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - David Whitmore
- Departments of Anaesthesia and Critical Care, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
- Countess of Chester Hospital NHS Foundation Trust, Chester, UK
| | - Pradeep Prabhu
- Department of Anaesthetics, The Royal Surrey Foundation NHS Trust, Guildford, UK
| | - David Timbrell
- Department of Anaesthetics, The Royal Surrey Foundation NHS Trust, Guildford, UK
- Anaesthetic Department, Frimley Park Hospital, Frimley Health NHS Foundation Trust, UK
| | - Sophie Allen
- Department of General Surgery, The Royal Surrey NHS Foundation Trust Hospital, Minimal Access Therapy Training Unit (MATTU), Guildford, UK
| | - Andrew O. Packham
- Department of Anaesthesia, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - David Sharpe
- Department of Gastro-Intestinal Surgery, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Helen Anderson
- Directorate of Anaesthesia, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Gary Minto
- Directorate of Anaesthesia, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Samuel McAleer
- Directorate of Anaesthesia, University Hospitals Plymouth NHS Trust, Plymouth, UK
- Emergency Medical Retrieval and Transfer Service, Cymru, Joint Hospital Group (Southwest), UK
| | - Stuart McPhail
- Directorate of Anaesthesia, University Hospitals Plymouth NHS Trust, Plymouth, UK
- Institute of Naval Medicine, Alverstoke, UK
| | - Mohamed Alasmar
- Salford Royal NHS Foundation Trust, Salford Royal, Salford, UK
- Division of Cancer Sciences, School of Medical Sciences, University of Manchester, UK
| | - Robert A. Hartley
- Salford Royal NHS Foundation Trust, Salford Royal, Salford, UK
- Division of Cancer Sciences, School of Medical Sciences, University of Manchester, UK
| | - Javed Sultan
- Department of General Surgery, The Royal Surrey NHS Foundation Trust Hospital, Minimal Access Therapy Training Unit (MATTU), Guildford, UK
- Salford Royal NHS Foundation Trust, Salford Royal, Salford, UK
- Division of Cancer Sciences, School of Medical Sciences, University of Manchester, UK
| | - Ben Grace
- School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Timothy J. Underwood
- School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- University Hospitals Southampton, Department of Surgery, Southampton, UK
| | - James Byrne
- University Hospitals Southampton, Department of Surgery, Southampton, UK
| | - Fergus Noble
- University Hospitals Southampton, Department of Surgery, Southampton, UK
| | - Jamie Kelly
- University Hospitals Southampton, Department of Surgery, Southampton, UK
| | - Gillian Ansell
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- University Hospitals Southampton, Department of Surgery, Southampton, UK
| | - Mark Edwards
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- University Hospitals Southampton, Department of Surgery, Southampton, UK
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12
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Kalajahi HG, Yari A, Amini M, Catal T, Ahmadpour Youshanlui M, Pourbagherian O, Zhmurov CS, Mokhtarzadeh A. Therapeutic effect of microRNA-21 on differentially expressed hub genes in gastric cancer based on systems biology. Sci Rep 2023; 13:21906. [PMID: 38081950 PMCID: PMC10713559 DOI: 10.1038/s41598-023-49225-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 12/05/2023] [Indexed: 12/18/2023] Open
Abstract
Gastric cancer (GC) is a leading cause of mortality for many people. Cancer's initiating factors are poorly understood. miR-21 has a crucial function in several malignancies, particularly GC. Furthermore, it has been shown that miR-21 is critical for the emergence and advancement of GC. This work intends to identify new genes which expression is associated with the activity of mir-21 in GC and to investigate the effect of downregulation of mir-21 on these genes and gastric tumorigenesis. We utilized the gene expression profiles of GCs from an Array database (GSE13911) from the Gene Expression Omnibus (GEO) dataset to find differentially expressed genes (DEGs) between control and gastric cancer groups. Using weighted gene correlation network analysis (WGCNA) in R, the Gene co-expression network was reconstructed. The microRNA-mRNA network was then reconstructed using the miRWalk database, and by investigating the microRNA-mRNA network, the genes that have an association with mir-21 were found. To implement the functional investigation, MKN and AGS cell lines were transfected with anti-miR-21 next. Subsequently, MTT proliferation was utilized to assess the cell's vitality. qRT-PCR was then used to evaluate the anticipated levels of gene expression in both GC cell lines. This study discovered and predicted CCL28, NR3C2, and SNYPO2 as the targets of miR-21 (GC), which are downregulated through gastric tumorigenesis, showing great potential as therapeutic and diagnostic targets. The suppression of miR-21 in gastric GC cells led to the inhibition of cell proliferation and decreased expression of CCL28, NR3C2, and SNYPO2 genes. This study established that miR-21, via downregulating these genes, contributes significantly to the development of GC. In addition, systems biology techniques identified CCL28, NR3C2, and SNYPO2 genes as possible GC surveillance and therapy components.
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Affiliation(s)
- Hesam Ghafouri Kalajahi
- Department of Molecular Biology and Genetics, Uskudar University, Uskudar, 34662, Istanbul, Turkey
| | - AmirHossein Yari
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Amini
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Tunc Catal
- Department of Molecular Biology and Genetics, Uskudar University, Uskudar, 34662, Istanbul, Turkey
| | | | - Omid Pourbagherian
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Cigdem Sezer Zhmurov
- Department of Molecular Biology and Genetics, Uskudar University, Uskudar, 34662, Istanbul, Turkey.
| | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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13
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Albuquerque RB, Borba MASM, Fernandes MSS, Filgueira TO, Martins DBG, Filho JLL, Castoldi A, Souto FO. Interleukin-33 Expression on Treatment Outcomes and Prognosis in Brazilian Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy. Int J Mol Sci 2023; 24:16326. [PMID: 38003516 PMCID: PMC10671081 DOI: 10.3390/ijms242216326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 10/30/2023] [Accepted: 11/01/2023] [Indexed: 11/26/2023] Open
Abstract
Interleukin-33 (IL-33), a member of the interleukin-1(IL-1) family of cytokines, remains poorly understood in the context of human breast cancer and its impact on treatment outcomes. This study aimed to elucidate IL-33 expression patterns within tumor samples from a cohort of Brazilian female breast cancer patients undergoing neoadjuvant chemotherapy while exploring its correlation with clinicopathological markers. In total, 68 samples were meticulously evaluated, with IL-33 expression quantified through a quantitative polymerase chain reaction. The findings revealed a substantial upregulation of IL-33 expression in breast cancer patient samples, specifically within the Triple-negative and Luminal A and B subtypes, when compared to controls (healthy breast tissues). Notably, the Luminal B subtype displayed a marked elevation in IL-33 expression relative to the Luminal A subtype (p < 0.05). Moreover, a progressive surge in IL-33 expression was discerned among Luminal subtype patients with TNM 4 staging criteria, further underscoring its significance (p < 0.005). Furthermore, chemotherapy-naïve patients of Luminal A and B subtypes exhibited heightened IL-33 expression (p < 0.05). Collectively, our findings propose that chemotherapy could potentially mitigate tumor aggressiveness by suppressing IL-33 expression in breast cancer, thus warranting consideration as a prognostic marker for gauging chemotherapy response and predicting disease progression in Luminal subtype patients. This study not only sheds light on the intricate roles of IL-33 in breast cancer but also offers valuable insights for future IL-33-related research endeavors within this context.
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Affiliation(s)
- Renata B. Albuquerque
- Keizo Asami Institute (iLIKA), Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil; (M.A.S.M.B.); (T.O.F.); (D.B.G.M.); (J.L.L.F.); (A.C.)
- Postgraduate Program in Biology Applied to Health, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil
| | - Maria Amélia S. M. Borba
- Keizo Asami Institute (iLIKA), Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil; (M.A.S.M.B.); (T.O.F.); (D.B.G.M.); (J.L.L.F.); (A.C.)
| | - Matheus S. S. Fernandes
- Postgraduate Program in Neuropsychiatry and Behavioral Sciences, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil;
| | - Tayrine O. Filgueira
- Keizo Asami Institute (iLIKA), Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil; (M.A.S.M.B.); (T.O.F.); (D.B.G.M.); (J.L.L.F.); (A.C.)
- Postgraduate Program in Biology Applied to Health, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil
| | - Danyelly Bruneska G. Martins
- Keizo Asami Institute (iLIKA), Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil; (M.A.S.M.B.); (T.O.F.); (D.B.G.M.); (J.L.L.F.); (A.C.)
- Postgraduate Program in Biology Applied to Health, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil
| | - José Luiz L. Filho
- Keizo Asami Institute (iLIKA), Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil; (M.A.S.M.B.); (T.O.F.); (D.B.G.M.); (J.L.L.F.); (A.C.)
- Postgraduate Program in Biology Applied to Health, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil
| | - Angela Castoldi
- Keizo Asami Institute (iLIKA), Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil; (M.A.S.M.B.); (T.O.F.); (D.B.G.M.); (J.L.L.F.); (A.C.)
- Postgraduate Program in Biology Applied to Health, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil
- Life Sciences Nucleus, Academic Center, Federal University of Pernambuco (UFPE), Rodovia BR-104, Km 59, s/n, Caruaru 55002-970, PE, Brazil
| | - Fabrício Oliveira Souto
- Keizo Asami Institute (iLIKA), Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil; (M.A.S.M.B.); (T.O.F.); (D.B.G.M.); (J.L.L.F.); (A.C.)
- Postgraduate Program in Biology Applied to Health, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Recife 50670-901, PE, Brazil
- Life Sciences Nucleus, Academic Center, Federal University of Pernambuco (UFPE), Rodovia BR-104, Km 59, s/n, Caruaru 55002-970, PE, Brazil
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14
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Ishtiaq A, Nasrullah MA, Khan JS, Malik S, Tareen U, Anees M, Sultan A, Murtaza I. A cohort study investigating the role of Bisphenol A in the molecular pathogenesis of breast cancer. J Cancer Res Clin Oncol 2023; 149:14565-14575. [PMID: 37580403 DOI: 10.1007/s00432-023-05247-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 08/02/2023] [Indexed: 08/16/2023]
Abstract
BACKGROUND Breast cancer is an abnormal division of breast cells. Bisphenol A (BPA), an environmental toxicant, is identified as an emerging risk factor for breast cancer development. However, to the best of our knowledge, no previous study has investigated the BPA levels in breast cancer patients in Pakistan. The present study sought to explore the role of BPA in tumor growth among the Pakistani population. METHODS The levels of BPA were analyzed in the serum samples of breast cancer patients and controls by using HPLC. To elucidate the role of BPA to initiate tumorigenic events in breast tissue different biochemical assays along with expression analysis of tumor markers were performed. RESULTS The level of BPA in the serum samples of breast cancer patients was significantly higher than control. Histological analysis of breast cancer tissue samples revealed distinct subtypes of tumor, such as ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). There was a significant increase in ROS level while a significant decrease in the levels of superoxide dismutase (SOD) and catalase (CAT) enzymes in malignant breast tissue samples as compared to control tissue samples. We found upregulated expression of p53, ZEB1 and WNT1 genes at mRNA level in malignant breast tissue samples by 17 folds, 328 folds and 35 folds, respectively. p53 protein expression in malignant breast tissue samples was also enhanced at the translational level. CONCLUSION Current findings suggest a relationship between BPA and the progression of breast cancer among the Pakistani population.
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Affiliation(s)
- Ayesha Ishtiaq
- Signal Transduction Laboratory, Department of Biochemistry, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan.
| | - Maryam Anyat Nasrullah
- Department of Biochemistry, Quaid-I-Azam University Islamabad, Islamabad, 45320, Pakistan
| | | | - Sara Malik
- Rawalpindi Medical University, Rawalpindi, Pakistan
| | - Usman Tareen
- Department of Biochemistry, Quaid-I-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Mariam Anees
- Department of Biochemistry, Quaid-I-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Aneesa Sultan
- Department of Biochemistry, Quaid-I-Azam University Islamabad, Islamabad, 45320, Pakistan.
| | - Iram Murtaza
- Signal Transduction Laboratory, Department of Biochemistry, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan.
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张 敏, 刘 生, 张 诺, 张 文, 夏 勇, 宋 雪, 张 小, 左 芦, 李 静, 胡 建. [High expression of RAB7A is associated with poor prognosis of gastric cancer by promoting tumor invasion]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2023; 43:1734-1743. [PMID: 37933649 PMCID: PMC10630196 DOI: 10.12122/j.issn.1673-4254.2023.10.11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Indexed: 11/08/2023]
Abstract
OBJECTIVE To explore the expression level of Ras-related protein 7A (RAB7A) in gastric cancer and its prognostic implications. METHODS Based on data from public databases and a cohort of 104 patients undergoing radical gastrectomy for gastric cancer in our hospital, we analyzed RAB7A expression level in gastric cancer and adjacent tissues and its association with clinicopathological parameters and prognosis of the patients. Bioinformatic analysis was performed to predict the pathways of RAB7A to affect gastric cancer invasion. In gastric cancer MGC803 cells with lentivirus-mediated interference or overexpression of RAB7A, the changes in extracellular matrix (ECM) degradation and cell migration and invasion were analyzed using immunoblotting, wound healing assay and Transwell experiments. RESULTS The data from public cancer databases and clinical samples showed a significantly higher expression of RAB7A in gastric cancer tissues than in normal or adjacent tissues (P<0.01) with a close correlation with a poorer patient survival (P<0.01) and a positive correlation with serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels (P<0.001). Univariate and multivariate Cox regression analyses suggested that a high RAB7A expression was an independent risk factor affecting the 5-year survival rate of gastric cancer patients (HR: 2.882; 95% CI: 1.459-5.693). ROC curve analysis showed that at the cut-off value of 2.625, RAB7A expression level had a sensitivity of 84.62% and a specificity of 71.15% for predicting postoperative 5-year mortality of the patients. Bioinformatic analysis suggested that RAB7A was involved in ECM degradation and activation of PI3K/AKT signaling in gastric cancer. MGC803 cells with RAB7A overexpression showed activation of the PI3K/AKT signaling pathway (P<0.01) with enhanced expressions of MMP-2 and MMP-9 (P<0.01) and cell migration and invasion capacities (P<0.01). CONCLUSION RAB7A is highly expressed in gastric cancer tissues and affects the patients' prognosis possibly by activating the PI3K/AKT signaling pathway and enhancing ECM degradation to promote tumor invasion.
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Affiliation(s)
- 敏 张
- 蚌埠医学院第一附属医院检验科，安徽 蚌埠 233000Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
- 蚌埠医学院检验医学院，安徽 蚌埠 233000School of Laboratory Medicine, Bengbu Medical College, Bengbu 233000, China
| | - 生宝 刘
- 蚌埠医学院检验医学院，安徽 蚌埠 233000School of Laboratory Medicine, Bengbu Medical College, Bengbu 233000, China
- 蚌埠医学院第一附属医院病理科，安徽 蚌埠 233000Department of Pathology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
| | - 诺 张
- 蚌埠医学院第一附属医院检验科，安徽 蚌埠 233000Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
- 蚌埠医学院检验医学院，安徽 蚌埠 233000School of Laboratory Medicine, Bengbu Medical College, Bengbu 233000, China
| | - 文静 张
- 蚌埠医学院第一附属医院检验科，安徽 蚌埠 233000Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
- 蚌埠医学院检验医学院，安徽 蚌埠 233000School of Laboratory Medicine, Bengbu Medical College, Bengbu 233000, China
| | - 勇生 夏
- 蚌埠医学院第一附属医院胃肠外科，安徽 蚌埠 233000Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
| | - 雪 宋
- 蚌埠医学院第一附属医院中心实验室，安徽 蚌埠 233000Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
| | - 小凤 张
- 蚌埠医学院第一附属医院中心实验室，安徽 蚌埠 233000Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
| | - 芦根 左
- 蚌埠医学院第一附属医院胃肠外科，安徽 蚌埠 233000Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
| | - 静 李
- 蚌埠医学院第一附属医院检验科，安徽 蚌埠 233000Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
| | - 建国 胡
- 蚌埠医学院第一附属医院检验科，安徽 蚌埠 233000Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
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Chekhun V, Martynyuk О, Lukianova Y, Mushii O, Zadvornyi T, Lukianova N. FEATURES OF BREAST CANCER IN PATIENTS OF YOUNG AGE: SEARCH FOR DIAGNOSIS OPTIMIZATION AND PERSONALIZED TREATMENT. Exp Oncol 2023; 45:139-150. [PMID: 37824778 DOI: 10.15407/exp-oncology.2023.02.139] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Indexed: 10/14/2023]
Abstract
The statistical data of the recent decades demonstrate a rapid growth of breast cancer (BCa) incidence and a tendency toward its increase especially in young women. In the structure of morbidity of women in the age group of 18-29 years, BCa ranks first and in the age range of 15-39 years, BCa is one of the leading causes of mortality. According to the data of the epidemiological and clinical studies, the young age is an independent unfavorable prognostic factor of BCa that is associated with an unfavorable prognosis and low survival rates and is considered an important predictor of the disease aggressiveness, a high risk of metastasis and recurrence. The variability of clinicopathological and molecular-biological features of BCa in patients of different age groups as well as the varying course of the disease and different responses to the therapy are mediated by many factors. The analysis of the literature data on the factors and mechanisms of BCa initiation in patients of different age groups demonstrates that the pathogen- esis of BCa depends not only on the molecular-genetic alterations but also on the metabolic disorders caused by the current social and household rhythm of life and nutrition peculiarities. All these factors affect both the general con- dition of the body and the formation of an aggressive microenvironment of the tumor lesion. The identified features of transcriptome and the differential gene expression give evidence of different regulations of the immune response and the metabolic processes in BCa patients of different age groups. Association between the high expression of the components of the stromal microenvironment and the inflammatory immune infiltrate as well as the increased vascu- larization of the tumor lesion has been found in BCa tissue of young patients. Proving the nature of the formation of the landscape comprising molecular-genetic, cytokine, and immune factors of the tumor microenvironment will undoubtedly contribute to our understanding of the mechanisms of tumor growth allowing for the development of algorithms for delineating the groups at high risk of tumor progression, which requires more careful monitoring and personalized treatment approach. Th s will be helpful in the development of innovative technologies for complex BCa treatment.
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Affiliation(s)
- V Chekhun
- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, 03022 Kyiv, Ukraine.
| | - О Martynyuk
- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, 03022 Kyiv, Ukraine
| | - Ye Lukianova
- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, 03022 Kyiv, Ukraine
| | - O Mushii
- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, 03022 Kyiv, Ukraine
| | - T Zadvornyi
- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, 03022 Kyiv, Ukraine
| | - N Lukianova
- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, 03022 Kyiv, Ukraine
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Ghiasi H, Khaldari M, Taherkhani R. Identification of hub genes associated with somatic cell score in dairy cow. Trop Anim Health Prod 2023; 55:349. [PMID: 37796357 DOI: 10.1007/s11250-023-03766-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 09/19/2023] [Indexed: 10/06/2023]
Abstract
CONTEXT Somatic cell count (SCC) is used as an indicator of udder health. The log transformation of SCC is called somatic cell score (SCS). AIM Several QTL and genes have been identified that are associated with SCS. This study aimed to identify the most important genes associated with SCS. METHODS This study compiled 168 genes that were reported to be significantly linked to SCS. Pathway analysis and network analysis were used to identify hub genes. KEY RESULTS Pathway analysis of these genes identified 73 gene ontology (GO) terms associated with SCS. These GO terms are associated with molecular function, biological processes, and cellular components, and the identified pathways are directly or indirectly linked with the immune system. In this study, a gene network was constructed, and from this network, the 17 hub genes (CD4, CXCL8, TLR4, STAT1, TLR2, CXCL9, CCR2, IGF1, LEP, SPP1, GH1, GHR, VWF, TNFSF11, IL10RA, NOD2, and PDGFRB) associated to SCS were identified. The subnetwork analysis yielded 10 clusters, with cluster 1 containing all identified hub genes (except for the VWF gene). CONCLUSION Most hub genes and pathways identified in our study were mainly involved in inflammatory and cytokine responses. IMPLICATIONS Result obtained in current study provides knowledge of the genetic basis and biological mechanisms controlling SCS. Therefore, the identified hub genes may be regarded as the main gene for the genomic selection of mastitis resistance.
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Affiliation(s)
- Heydar Ghiasi
- Department of Animal Science, Faculty of Agricultural Science, Payame Noor University, Tehran, 19395-4697, Iran.
| | - Majid Khaldari
- Department of Animal Science, Faculty of Agriculture, Lorestan University, Khorram-Abad, Iran
| | - Reza Taherkhani
- Department of Animal Science, Faculty of Agricultural Science, Payame Noor University, Tehran, 19395-4697, Iran
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18
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Thuc Nguyen TM, Dinh Le R, Nguyen CV. Breast cancer molecular subtype and relationship with clinicopathological profiles among Vietnamese women: A retrospective study. Pathol Res Pract 2023; 250:154819. [PMID: 37748212 DOI: 10.1016/j.prp.2023.154819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 09/13/2023] [Accepted: 09/14/2023] [Indexed: 09/27/2023]
Abstract
BACKGROUND Molecular subtypes play an important role in predicting prognosis and guiding treatment for breast cancer. Having a better knowledge of ethnic molecular features is essential. OBJECTIVES Determining the distribution of various breast cancer molecular subtypes and investigating the relationship between these subtypes and clinicopathological features. METHODS Retrospective data was collected from Hanoi National Cancer Hospital and Bach Mai Hospital that included 274 women diagnosed with invasive breast cancer between January 2017 and June 2019. Patients were categorized into five subtypes according to the 2015 St. Gallen molecular classification. The variables analyzed were molecular subtypes and tumor-related characteristics. To evaluate the relationship between these subtypes and clinicopathological features, a Chi-squared test and Fisher exact test were performed. RESULTS The most prominent subtype was Luminal A (33.2%), followed by Luminal B/Her2- (19.7%) and Luminal B/Her2 + (17.5%), then HER2 overexpression (16.4%), whereas triple negative was the least popular subtype (13.1%). Particularly, 33.9% of all patients, including the Luminal B/Her2 + and the HER2 overexpressing groups, were Her2 positive. There was a statistically significant difference between molecular subtypes and histological type (p = 0.01), tumor grade (p < 0.001), but it was independent of age, tumor size, lymph node metastasis, and lymphovascular invasion. CONCLUSIONS In contrast to the triple negative variant, the Luminal A variant is the most common among Vietnamese women. The rate of positive tests for HER2 was rather high. These subtypes were closely related to tumor grade and histopathological type. Understanding the molecular subtypes and their relation to clinicopathological features helps clinicians with patient treatment, and prognosis. The application of the 2015 St. Gallen molecular classification should be recommended for use in clinical practice.
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Affiliation(s)
| | | | - Chu Van Nguyen
- Ha Noi Medical University, Viet Nam; National Cancer Hospital, Ha Noi, Viet Nam
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Park YH, Im SA, Park K, Wen J, Lee KH, Choi YL, Lee WC, Min A, Bonato V, Park S, Ram S, Lee DW, Kim JY, Lee SK, Lee WW, Lee J, Kim M, Kim HS, Weinrich SL, Ryu HS, Kim TY, Dann S, Kim YJ, Fernandez DR, Koh J, Wang S, Park SY, Deng S, Powell E, Ravi RK, Bienkowska J, Rejto PA, Park WY, Kan Z. Longitudinal multi-omics study of palbociclib resistance in HR-positive/HER2-negative metastatic breast cancer. Genome Med 2023; 15:55. [PMID: 37475004 PMCID: PMC10360358 DOI: 10.1186/s13073-023-01201-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 06/05/2023] [Indexed: 07/22/2023] Open
Abstract
BACKGROUND Cyclin-dependent kinase 4/6 inhibitor (CDK4/6) therapy plus endocrine therapy (ET) is an effective treatment for patients with hormone receptor-positive/human epidermal receptor 2-negative metastatic breast cancer (HR+/HER2- MBC); however, resistance is common and poorly understood. A comprehensive genomic and transcriptomic analysis of pretreatment and post-treatment tumors from patients receiving palbociclib plus ET was performed to delineate molecular mechanisms of drug resistance. METHODS Tissue was collected from 89 patients with HR+/HER2- MBC, including those with recurrent and/or metastatic disease, receiving palbociclib plus an aromatase inhibitor or fulvestrant at Samsung Medical Center and Seoul National University Hospital from 2017 to 2020. Tumor biopsy and blood samples obtained at pretreatment, on-treatment (6 weeks and/or 12 weeks), and post-progression underwent RNA sequencing and whole-exome sequencing. Cox regression analysis was performed to identify the clinical and genomic variables associated with progression-free survival. RESULTS Novel markers associated with poor prognosis, including genomic scar features caused by homologous repair deficiency (HRD), estrogen response signatures, and four prognostic clusters with distinct molecular features were identified. Tumors with TP53 mutations co-occurring with a unique HRD-high cluster responded poorly to palbociclib plus ET. Comparisons of paired pre- and post-treatment samples revealed that tumors became enriched in APOBEC mutation signatures, and many switched to aggressive molecular subtypes with estrogen-independent characteristics. We identified frequent genomic alterations upon disease progression in RB1, ESR1, PTEN, and KMT2C. CONCLUSIONS We identified novel molecular features associated with poor prognosis and molecular mechanisms that could be targeted to overcome resistance to CKD4/6 plus ET. TRIAL REGISTRATION ClinicalTrials.gov, NCT03401359. The trial was posted on 18 January 2018 and registered prospectively.
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Affiliation(s)
- Yeon Hee Park
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
- Department of Health Science and Technology, School of Medicine & SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
| | - Seock-Ah Im
- Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea.
| | - Kyunghee Park
- Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea
| | - Ji Wen
- Oncology Research & Development, Pfizer Inc, San Diego, CA, USA
| | - Kyung-Hun Lee
- Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Yoon-La Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Health Science and Technology, School of Medicine & SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
| | - Won-Chul Lee
- Oncology Research & Development, Pfizer Inc, San Diego, CA, USA
| | - Ahrum Min
- Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | | | - Seri Park
- Department of Health Science and Technology, School of Medicine & SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
| | - Sripad Ram
- Drug Safety R&D, Pfizer Inc, San Diego, CA, USA
| | - Dae-Won Lee
- Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Ji-Yeon Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Su Kyeong Lee
- Research Center for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
| | - Won-Woo Lee
- Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Jisook Lee
- Oncology Research & Development, Pfizer Inc, San Diego, CA, USA
| | - Miso Kim
- Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | | | | | - Han Suk Ryu
- Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Tae Yong Kim
- Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Stephen Dann
- Oncology Research & Development, Pfizer Inc, San Diego, CA, USA
| | - Yu-Jin Kim
- Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | | | - Jiwon Koh
- Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Shuoguo Wang
- Oncology Research & Development, Pfizer Inc, San Diego, CA, USA
| | - Song Yi Park
- Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | | | - Eric Powell
- Oncology Research & Development, Pfizer Inc, San Diego, CA, USA
| | | | | | - Paul A Rejto
- Oncology Research & Development, Pfizer Inc, San Diego, CA, USA
| | - Woong-Yang Park
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Health Science and Technology, School of Medicine & SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
- Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea
| | - Zhengyan Kan
- Oncology Research & Development, Pfizer Inc, San Diego, CA, USA.
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Ferreira T, Gama A, Seixas F, Faustino-Rocha AI, Lopes C, Gaspar VM, Mano JF, Medeiros R, Oliveira PA. Mammary Glands of Women, Female Dogs and Female Rats: Similarities and Differences to Be Considered in Breast Cancer Research. Vet Sci 2023; 10:379. [PMID: 37368765 DOI: 10.3390/vetsci10060379] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/23/2023] [Accepted: 05/27/2023] [Indexed: 06/29/2023] Open
Abstract
Breast cancer is one of the most common and well-known types of cancer among women worldwide and is the most frequent neoplasm in intact female dogs. Female dogs are considered attractive models or studying spontaneous breast cancer, whereas female rats are currently the most widely used animal models for breast cancer research in the laboratory context. Both female dogs and female rats have contributed to the advancement of scientific knowledge in this field, and, in a "One Health" approach, they have allowed broad understanding of specific biopathological pathways, influence of environmental factors and screening/discovery of candidate therapies. This review aims to clearly showcase the similarities and differences among woman, female dog and female rat concerning to anatomical, physiological and histological features of the mammary gland and breast/mammary cancer epidemiology, in order to better portray breast tumorigenesis, and to ensure appropriate conclusions and extrapolation of results among species. We also discuss the major aspects that stand out in these species. The mammary glands of female dogs and women share structural similarities, especially with respect to the lactiferous ducts and lymphatic drainage. In contrast, female rats have only one lactiferous duct per nipple. A comprehensive comparison between humans and dogs is given a special focus, as these species share several aspects in terms of breast/mammary cancer epidemiology, such as age of onset, hormonal etiology, risk factors, and the clinical course of the disease. Holistically, it is clear that each species has advantages and limitations that researchers must consider during the development of experimental designs and data analysis.
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Affiliation(s)
- Tiago Ferreira
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
- Department of Chemistry, CICECO-Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
| | - Adelina Gama
- Animal and Veterinary Research Centre (CECAV), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
| | - Fernanda Seixas
- Animal and Veterinary Research Centre (CECAV), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
| | - Ana I Faustino-Rocha
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- Department of Zootechnics, School of Sciences and Technology, University of Évora, 7004-516 Évora, Portugal
- Comprehensive Health Research Center, 7004-516 Évora, Portugal
| | - Carlos Lopes
- Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal
| | - Vítor M Gaspar
- Department of Chemistry, CICECO-Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
| | - João F Mano
- Department of Chemistry, CICECO-Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
- Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal
- Research Department of the Portuguese League against Cancer-Regional Nucleus of the North (Liga Portuguesa Contra o Cancro-Núcleo Regional do Norte), 4200-177 Porto, Portugal
- Virology Service, Portuguese Institute of Oncology (IPO), 4200-072 Porto, Portugal
- Biomedical Research Center (CEBIMED), Faculty of Health Sciences of the Fernando Pessoa University, 4249-004 Porto, Portugal
| | - Paula A Oliveira
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
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Kuziel G, Moore BN, Arendt LM. Obesity and Fibrosis: Setting the Stage for Breast Cancer. Cancers (Basel) 2023; 15:cancers15112929. [PMID: 37296891 DOI: 10.3390/cancers15112929] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 05/22/2023] [Accepted: 05/23/2023] [Indexed: 06/12/2023] Open
Abstract
Obesity is a rising health concern and is linked to a worsened breast cancer prognosis. Tumor desmoplasia, which is characterized by elevated numbers of cancer-associated fibroblasts and the deposition of fibrillar collagens within the stroma, may contribute to the aggressive clinical behavior of breast cancer in obesity. A major component of the breast is adipose tissue, and fibrotic changes in adipose tissue due to obesity may contribute to breast cancer development and the biology of the resulting tumors. Adipose tissue fibrosis is a consequence of obesity that has multiple sources. Adipocytes and adipose-derived stromal cells secrete extracellular matrix composed of collagen family members and matricellular proteins that are altered by obesity. Adipose tissue also becomes a site of chronic, macrophage-driven inflammation. Macrophages exist as a diverse population within obese adipose tissue and mediate the development of fibrosis through the secretion of growth factors and matricellular proteins and interactions with other stromal cells. While weight loss is recommended to resolve obesity, the long-term effects of weight loss on adipose tissue fibrosis and inflammation within breast tissue are less clear. Increased fibrosis within breast tissue may increase the risk for tumor development as well as promote characteristics associated with tumor aggressiveness.
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Affiliation(s)
- Genevra Kuziel
- Cancer Biology Graduate Program, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705, USA
| | - Brittney N Moore
- Department of Comparative Biosciences, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA
| | - Lisa M Arendt
- Cancer Biology Graduate Program, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705, USA
- Department of Comparative Biosciences, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA
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Kamran M, Khalid AB, Muneeb MD, Hussain S. Epidemiology of premalignant and malignant upper gastrointestinal lesions among patients presenting from a rural community in Karachi, Pakistan. Pak J Med Sci 2023; 39:858-862. [PMID: 37250557 PMCID: PMC10214813 DOI: 10.12669/pjms.39.3.7379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 12/17/2022] [Accepted: 02/22/2023] [Indexed: 08/30/2023] Open
Abstract
Objective Understanding the epidemiology of upper gastrointestinal cancers in Pakistan may help in identifying important demographic risk factors for upper gastrointestinal malignancies in a particular rural population group. This will benefit in implementing tailored prevention approaches as well as effective management of health services. Method A secondary data analysis of 1193 patients was conducted who went through diagnostic upper GI endoscopy between December 2016 to May 2019 at Fatima Hospital. The endoscopies were performed at Fatima Hospital which is the main health resource for the specifically targeted rural community. Data was analyzed using SPSS version 21. Results The median age of patients included in the sample was 35 years (IQR=20 years). One third of all endoscopic findings were concluded as normal. The frequency of malignant upper gastrointestinal lesions was relatively higher among male and patients with age 65 years or more. The study didn't find any significant differences in the distribution of malignancies on the basis of ethnicity. Adenocarcinoma of esophagus was the most common malignant lesion. Conclusion The average age of patients undergoing upper gastrointestinal endoscopy among rural community of Karachi was relatively low. The burden of upper GI malignancies was significantly higher among elderly. Male patients had significantly greater burden of premalignant and malignant lesions as compared to females. No differences in the distribution of diagnostic outcomes were observed on the basis of ethnicity.
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Affiliation(s)
- Muhammad Kamran
- Muhammad Kamran, FCPS. Assistant Professor, Department of Medicine, Fatima Hospital, Baqai Medical University, Karachi, Pakistan
| | - Abdullah Bin Khalid
- Abdullah Bin Khalid, FCPS. Assistant Professor, National Institute of Liver & GI Diseases (NILGID), Dow University of Health Sciences, Karachi, Pakistan
| | - Muhammad Danish Muneeb
- Muhammad Danish Muneeb, FCPS. Associate Professor, Department of Surgery, Fatima Hospital, Baqai Medical University, Karachi, Pakistan
| | - Sohail Hussain
- Sohail Hussain, FCPS. Assistant Professor, Department of Gastroenterology, Ziauddin University, Karachi, Pakistan
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23
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Sarkar MS, Mia MM, Amin MA, Hossain MS, Islam MZ. Bioinformatics and network biology approach to identifying type 2 diabetes genes and pathways that influence the progression of breast cancer. Heliyon 2023; 9:e16151. [PMID: 37234659 PMCID: PMC10205526 DOI: 10.1016/j.heliyon.2023.e16151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 04/28/2023] [Accepted: 05/07/2023] [Indexed: 05/28/2023] Open
Abstract
Breast cancer is the second most prevalent malignancy affecting women. Postmenopausal women breast tumor is one of the top causes of death in women, accounting for 23% of cancer cases. Type 2 diabetes, a worldwide pandemic, has been connected to a heightened risk of several malignancies, although its association with breast cancer is still uncertain. In comparison to non-diabetic women, women with T2DM had a 23% elevated likelihood of developing breast cancer. It is difficult to determine causative or genetic susceptibility that connect T2DM and breast cancer. We created a large-scale network-based quantitative approach employing unbiased methods to discover abnormally amplified genes in both T2DM and breast cancer, to solve these issues. We performed transcriptome analysis to uncover identical genetic biomarkers and pathways to clarify the connection between T2DM and breast cancer patients. In this study, two RNA-seq datasets (GSE103001 and GSE86468) from the Gene Expression Omnibus (GEO) are used to identify mutually differentially expressed genes (DEGs) for breast cancer and T2DM, as well as common pathways and prospective medicines. Firstly, 45 shared genes (30 upregulated and 15 downregulated) between T2D and breast cancer were detected. We employed gene ontology and pathway enrichment to characterize prevalent DEGs' molecular processes and signal transduction pathways and observed that T2DM has certain connections to the progression of breast cancer. Using several computational and statistical approaches, we created a protein-protein interactions (PPI) network and revealed hub genes. These hub genes can be potential biomarkers, which may also lead to new therapeutic strategies for investigated diseases. We conducted TF-gene interactions, gene-microRNA interactions, protein-drug interactions, and gene-disease associations to find potential connections between T2DM and breast cancer pathologies. We assume that the potential drugs that emerged from this study could be useful therapeutic values. Researchers, doctors, biotechnologists, and many others may benefit from this research.
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Affiliation(s)
- Md Sumon Sarkar
- Department of Pharmacy, Islamic University, Kushtia-7003, Bangladesh
| | - Md Misor Mia
- Department of Pharmacy, Islamic University, Kushtia-7003, Bangladesh
| | - Md Al Amin
- Department of Computer Science & Engineering, Prime University, Dhaka-1216, Bangladesh
| | - Md Sojib Hossain
- Department of Mathematics, Govt. Bangla College, Dhaka-1216, Bangladesh
| | - Md Zahidul Islam
- Department of Information & Communication Technology, Islamic University, Kushtia-7003, Bangladesh
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Zhao H, Yan H, Chen L, Li Y. Development and validation of a predictive nomogram for the specific mortality risk of luminal B breast cancer patients: a competing risk model based on real populations. Transl Cancer Res 2023; 12:965-979. [PMID: 37180675 PMCID: PMC10175002 DOI: 10.21037/tcr-23-484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 04/23/2023] [Indexed: 05/16/2023]
Abstract
Background For clinical workers, disease-specific death is a better indicator of tumor severity. Breast cancer is the most prevalent malignancy in women. Luminol type B breast cancer is one of the biggest threats to women's health, and few studies have paid attention to its specific death. Early recognition of luminol type B breast cancer allows clinicians to assess the prognosis and develop more optimal treatment plans. Methods In this study, the basic information of luminal B population, clinical and pathological characteristics, treatment regimen and survival data were collected from the SEER database. The patients were randomly divided into a training group and a validation group. The single-factor and multi-factor competitive risk models were used to analyze the independent influencing factors of tumor-specific death, and the predictive nomogram based on the competitive risk model was constructed. The consistency index (C-index) and calibration curves over time were used to evaluate the accuracy of the predicted nomograms. Results This study included a total of 30,419 luminal B patient. The median follow-up period was 60 (IQR: 44-81) months. Among the 4,705 deaths during the follow-up period, 2,863 patients died specifically, accounting for 60.85% of the deaths. The independent predictive factors of cancer-specific mortality were: married, primary site, grade, stage, the primary site of operation, radiotherapy, chemotherapy, metastasis (lymph node, bone, brain, liver, lung), and Estrogen Receptor and Progesterone Receptor status. In the training cohort, the C-index of the predictive nomogram was 0.858, and the area under the receiver operating characteristic curve (AUC) for the first, third, and fifth years was 0.891, 0.864, and 0.845. The C-index of the validation cohort was 0.862, and the AUC for the first, third, and fifth years was 0.888, 0.872, and 0.849. The calibration curves of the training and validation cohorts showed that the predicted probability of the model was very consistent with the actual probability. And the 5-year survival rate according to the traditional survival analysis was 9.49%, while the 5-year specific mortality rate was only 8.88%. Conclusions The luminal B competing risk model we established has ideal accuracy and calibration.
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Affiliation(s)
- Huimin Zhao
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Haoxiang Yan
- Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Lianju Chen
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yafei Li
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Department of Cardiology, The Seventh People’s Hospital of Chongqing, Chongqing, China
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Hussain S, Durrani F, Khan A. Frequency and Clinicopathologic Characteristics of Triple-Negative Breast Cancer Among Breast Cancer Patients Presenting to Medical Oncology Department, Hayatabad Medical Complex Peshawar, Pakistan. Cureus 2023; 15:e34581. [PMID: 36883091 PMCID: PMC9985817 DOI: 10.7759/cureus.34581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/02/2023] [Indexed: 02/05/2023] Open
Abstract
INTRODUCTION Breast cancer is one of the most common cancers affecting females. The outcomes of this study will aid future research and policy suggestions by giving a rapid local burden and clinicopathologic profile of triple-negative breast cancer (TNBC) patients. MATERIAL AND METHODS This cross-sectional study was carried out at the Department of Oncology, Hayatabad Medical Complex Peshawar, Pakistan, from April 21, 2022, to October 21, 2022. The sample size was 120 using a 95% confidence level, 18.7% proportion of TNBC frequency in patients with breast cancer, and 7% absolute precision. All patients who presented with newly diagnosed breast cancer and were between the ages of 30-60 years were included in the study. The study excluded male patients and patients with a history of surgical intervention on the breast during the previous six months. RESULTS A total of 120 patients were evaluated. Age ranged between 30-60 years with a mean age of 45 years. Thirty-four (28%) patients were in the age range of 30-45 years and 86 (72%) patients were in the age range of 46-60 years. Fifty-six (47%) patients had BMI ≤27 kg/m2 while 64 (53%) had BMI >27 kg/m2. The use of oral contraceptives was noted in 25 (21%) patients. A total of 62 (52%) patients had breast cancer on the right side while 58 (48%) had it on the left side. CONCLUSION According to the results of our study, 14% of breast cancer patients had triple-negative disease.
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Affiliation(s)
- Shah Hussain
- Medical Oncology Unit, Hayatabad Medical Complex Peshawar, Peshawar, PAK
| | - Fakeeda Durrani
- Medical Oncology Unit, Hayatabad Medical Complex Peshawar, Peshawar, PAK
| | - Asif Khan
- Department of Medicine, Khyber Teaching Hospital, Peshawar, PAK
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He Y, Zhang J, Chen H, Zhou Y, Hong L, Ma Y, Chen N, Zhao W, Tong Z. Clinical significance and prognostic value of receptor conversion after neoadjuvant chemotherapy in breast cancer patients. Front Surg 2023; 9:1037215. [PMID: 36684294 PMCID: PMC9852345 DOI: 10.3389/fsurg.2022.1037215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 10/25/2022] [Indexed: 01/09/2023] Open
Abstract
The hormone receptor (HR) status and human epidermal growth hormone receptor 2 (HER2) status of patients with breast cancer may change following neoadjuvant chemotherapy (NAC). We retrospectively analyzed the clinical data of 294 patients with stage II/III breast cancer to evaluate the clinical significance and prognostic value of receptor transformation after NAC in breast cancer patients. Pathological complete response after NAC was achieved in 10.7% of patients. HR, estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 conversion rates were 9.2%, 6.5%, 13.0%, 4.4%, and 33.7%, respectively. Patients with stable HR (P = 0.01) and HER2 (P = 0.048) expression had more favorable overall survival (OS). Low or reduced Ki-67 expression was associated with better disease-free survival (DFS) (P < 0.001) and OS (P < 0.01). Multivariate analysis showed that the number of lymph nodes after NAC, HR conversion, and radiotherapy were independent prognostic factors for overall survival. HR conversion implied a higher risk of death [hazard ratio, 2.56 (95% confidence interval: 1.19-5.51); P = 0.016]. Patients with HR conversion after NAC who received endocrine therapy had better DFS (P = 0.674) and OS (P = 0.363) than those who did not receive endocrine therapy, even if the HR changed from positive to negative. In conclusion, pathological testing should be performed before and after NAC, and even patients with HR conversion after NAC might benefit from endocrine therapy.
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Affiliation(s)
- Yang He
- Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Department of Breast Cancer, Tianjin Cancer Hospital Airport Hospital, Tianjin, China
| | - Jing Zhang
- Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Department of Integrative Oncology, Tianjin Cancer Hospital Airport Hospital, Tianjin, China
| | - Hui Chen
- Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Department of Oncology, Characteristic Medical Center of PAP, Tianjin, China
| | - Ying Zhou
- Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Department of Integrative Oncology, Tianjin Cancer Hospital Airport Hospital, Tianjin, China
| | - Liping Hong
- Center for Precision Cancer Medicine and Translational Research, Tianjin Cancer Hospital Airport Hospital, Tianjin, China
| | - Yue Ma
- The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Nannan Chen
- Department of Breast Cancer, Tianjin Cancer Hospital Airport Hospital, Tianjin, China
| | - Weipeng Zhao
- Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Zhongsheng Tong
- Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Correspondence: Zhongsheng Tong
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Yang F, He Q, Dai X, Zhang X, Song D. The potential role of nanomedicine in the treatment of breast cancer to overcome the obstacles of current therapies. Front Pharmacol 2023; 14:1143102. [PMID: 36909177 PMCID: PMC9992554 DOI: 10.3389/fphar.2023.1143102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 02/13/2023] [Indexed: 02/24/2023] Open
Abstract
Breast cancer (BC) is the most frequently diagnosed malignant tumor among women in the world. BC is the heterogeneous tumor with different subtypes including luminal A-like, luminal B-like (HER2-/HER2+), HER2 enriched, and triple-negative BC. The therapeutic strategies including surgery, chemotherapy, radiotherapy, targeted therapy, and endocrine therapy are well developed and commonly used in the treatment of BC. However, some adverse effects of these conventional treatments limited their wide application in clinical. Therefore, it is necessary to develop more safe and more efficient individualized treatment strategies of the BC. Nanomedicine, as the most promising strategy for controlled and targeted drug delivery, is widely used in multiple aspects of cancer therapy. Importantly, accumulative evidences show that nanomedicine has achieved good outcomes in the treatment of BC and a huge amount of BC patients benefited from the nanomedicine related treatments. In this review, we summarized and discussed the major problems occurred during the administration of conventional treatment strategies for BC and the potential roles of nanomedicine in promoting the treatment efficacy of BC by overcoming obstacles of current treatment of BC.
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Affiliation(s)
- Fan Yang
- Breast Surgery Department of General Surgery, The First Hospital of Jilin University, Changchun, China.,Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital of Jilin University, Changchun, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital of Jilin University, Changchun, China
| | - Qingjie He
- Breast Surgery Department of General Surgery, The First Hospital of Jilin University, Changchun, China.,Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital of Jilin University, Changchun, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital of Jilin University, Changchun, China
| | - Xiangpeng Dai
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital of Jilin University, Changchun, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital of Jilin University, Changchun, China
| | - Xiaoling Zhang
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital of Jilin University, Changchun, China.,National-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital of Jilin University, Changchun, China
| | - Dong Song
- Breast Surgery Department of General Surgery, The First Hospital of Jilin University, Changchun, China
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Akheel M, Senthilmurugan M, Jain A, Chahwala Q, Sherlin HJ, Wadhwania A. Incorporating the epidermal growth factor receptor expression and histopathological parameters in a mathematical model to predict the prognosis of oral squamous cell carcinoma: a prospective observational cohort study. J Maxillofac Oral Surg 2022; 21:1065-1073. [PMID: 36896074 PMCID: PMC9989106 DOI: 10.1007/s12663-022-01797-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 09/13/2022] [Indexed: 10/14/2022] Open
Abstract
Background Oral squamous cell carcinomas (OSCC) are the most common type of variant causing oral cancers, contributing for around 90%. The overall survival of these patients is below 50%. The postoperative overall survival (OS) has not improved over years much despite of advanced surgical techniques and invention of various anticancer drugs. There was always a requirement for a non-invasive molecular marker to predict the prognosis of these patients. The epidermal growth factor and their receptors are not only thought to play a critical but also an influential role in growth of the cell and differentiation in normal/ healthy tissues. They also play an important role in malignant progression of disease and tumorigenesis. A better and sound understanding of mechanisms at molecular level and identification of potential oncogenes in OSCC may provide innovative therapeutic decisions such as targeted therapy in management of these cancer patients. Aim & objectives The aim of this study is to check whether epidermal growth factor expression is a prognosticator in oral squamous cell carcinoma and also to propose a mathematical model to find the prognosis of the patients which have not been done so far in the literature. Materials & methods The study was a prospective cohort study with 25 patients who had biopsy proven OSCC who reported to our hospital from July 2017 to June 2019. The data collected from their histopathological report for this prospective study and model were: surgical margins (superior, inferior, anterior and posterior), depth of tumor, lymph nodal metastasis, lymphovascular invasion and scoring of epidermal growth factor receptor (EGFR) expression done by immunohistochemistry (IHC) on wax blocks. Results EGFR expression on surgical margins was found to have a p-value of 0.023 which was significant statistically. EGFR expression showed a statistically significant p value 0.002 as independent marker in prognosis with sensitivity of 97.7% and specificity of 61.2%. The tumor depth of infiltration showed an insignificant correlation with pathological Tumor, Node, Metastasis (TNM) staging with a p value of 0.860. A mathematical model linear regression equation was proposed which predicted a cutoff value above 16, the prognosis of the patient being bad (Stages III and IV), and below 16, the prognosis of the patient being good (Stages I and II). Conclusion This study put forward a proposed mathematical model by incorporating all important parameters to predict the prognosis of the patients. EGFR expression is one such important parameter to be considered to develop anti-EGFR agents to improve the OS of the patients. Supplementary Information The online version contains supplementary material available at 10.1007/s12663-022-01797-0.
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Affiliation(s)
- Mohammad Akheel
- Oral & Maxillofacial Surgery, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu India
| | - M. Senthilmurugan
- Dept of Oral Oncology, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu India
| | - Amit Jain
- SRJ-CBCC Cancer Centre, Indore, India
| | | | - Herald J. Sherlin
- Dept of Pathology, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu India
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Lucia Ruiz Benitez M, Severo Sabedra Sousa F, Peter Furtado I, Carlos Rodrigues Junior J, Victoria Mascarenhas Borba M, Vieira Segatto N, Tabarelli G, Klein Couto G, Júlia Damé Fonseca Paschoal M, Silveira Pacheco B, E. D. Rodrigues O, Collares T, Kömmling Seixas F. Chiral β‐arylchalcogenium azide induce apoptosis and regulate Oxidative Damage on Human Bladder Cancer Cells. ChemistrySelect 2022. [DOI: 10.1002/slct.202203207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Martha Lucia Ruiz Benitez
- Laboratory of Cancer Biotechnology, Technology Development Center Federal University of Pelotas Pelotas Rio Grande do Sul Brazil
- School of Basic and Biomedical Sciences Universidad Simón Bolívar Barranquilla Colombia
| | - Fernanda Severo Sabedra Sousa
- Laboratory of Cancer Biotechnology, Technology Development Center Federal University of Pelotas Pelotas Rio Grande do Sul Brazil
| | - Izadora Peter Furtado
- Laboratory of Cancer Biotechnology, Technology Development Center Federal University of Pelotas Pelotas Rio Grande do Sul Brazil
| | - João Carlos Rodrigues Junior
- Laboratory of Cancer Biotechnology, Technology Development Center Federal University of Pelotas Pelotas Rio Grande do Sul Brazil
| | - Msc. Victoria Mascarenhas Borba
- Laboratory of Cancer Biotechnology, Technology Development Center Federal University of Pelotas Pelotas Rio Grande do Sul Brazil
| | - Natália Vieira Segatto
- Laboratory of Cancer Biotechnology, Technology Development Center Federal University of Pelotas Pelotas Rio Grande do Sul Brazil
| | - Greice Tabarelli
- LabSelen-NanoBio - Chemistry Department Federal University of Santa Maria, Santa Maria Rio Grande do Sul Brazil
| | - Gabriela Klein Couto
- Laboratory of Cancer Biotechnology, Technology Development Center Federal University of Pelotas Pelotas Rio Grande do Sul Brazil
| | - Msc. Júlia Damé Fonseca Paschoal
- Laboratory of Cancer Biotechnology, Technology Development Center Federal University of Pelotas Pelotas Rio Grande do Sul Brazil
| | - Bruna Silveira Pacheco
- Laboratory of Cancer Biotechnology, Technology Development Center Federal University of Pelotas Pelotas Rio Grande do Sul Brazil
| | - Oscar E. D. Rodrigues
- LabSelen-NanoBio - Chemistry Department Federal University of Santa Maria, Santa Maria Rio Grande do Sul Brazil
| | - Tiago Collares
- Laboratory of Cancer Biotechnology, Technology Development Center Federal University of Pelotas Pelotas Rio Grande do Sul Brazil
| | - Fabiana Kömmling Seixas
- Laboratory of Cancer Biotechnology, Technology Development Center Federal University of Pelotas Pelotas Rio Grande do Sul Brazil
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Expression and Signaling Pathways of Nerve Growth Factor (NGF) and Pro-NGF in Breast Cancer: A Systematic Review. Curr Oncol 2022; 29:8103-8120. [PMID: 36354700 PMCID: PMC9689427 DOI: 10.3390/curroncol29110640] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 10/19/2022] [Accepted: 10/25/2022] [Indexed: 11/07/2022] Open
Abstract
Breast cancer represents the most common type of cancer and is the leading cause of death due to cancer among women. Thus, the prevention and early diagnosis of breast cancer is of primary urgency, as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor involved in the regulation of neuronal functions through the binding of the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). In addition, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin, or by binding to TrkA receptors with low affinity. Several examples of in vitro and in vivo evidence show that NGF is both synthesized and released by breast cancer cells, and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signaling has been related to breast cancer invasion and metastasis. Other studies suggested that NGF and its receptors could represent a good diagnostic and prognostic tool, as well as promising therapeutic targets for breast cancer. In this paper, we comprehensively summarize and systematically review the current experimental evidence on this topic. INPLASY ID: INPLASY2022100017.
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Meghalatha TS, Muninathan N. Antitumor activity of withaferin-A and propolis in benz (a) pyrene-induced breast cancer. Bioinformation 2022; 18:841-844. [PMID: 37426503 PMCID: PMC10326326 DOI: 10.6026/97320630018841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 09/30/2022] [Accepted: 09/30/2022] [Indexed: 09/28/2024] Open
Abstract
Female breast cancer is the leading malignancy surpassing lung cancer recently, and its incidence is continued to rise in many countries. The existing anticancer drugs have limitations like drug resistance and adverse effects leading to poor clinical outcomes. The natural compounds withaferin-A and propolis have been individually reported for their anticancer activity in preclinical models. However, the combined effect of these compounds has not been studied especially in breast cancer models. Therefore, it is of interest to evaluate the effect of Withaferin-A and propolis on Benz(a)pyrene-induced breast cancer. Wistar rats of female gender were treated with saline (normal control), Benz(a)pyrene (disease control), Benz(a)pyrene+ Withaferin-A or Propolis, Benz(a)pyrene+ Withaferin-A+ Propolis. At the end of the treatment, the plasma levels of carcino embryonic antigen (CEA) were measured. We observed a decrease in carcino embryonic antigen (CEA) levels in rats received withaferin-A and propolis combination rather than individual compounds indicating their beneficial role in breast cancer. Results of the present study show that propolis, when combined with withaferin A, exhibits better anti tumor activity than its individual effect in Benz (a) pyrene-induced mammary carcinogenesis.
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Affiliation(s)
- Thazhathuputhenpurayil Sadhasivan Meghalatha
- Central Research Laboratory, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research, Kanchipuram Tamil Nadu, India – 631552
| | - Natarajan Muninathan
- Central Research Laboratory, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research, Kanchipuram Tamil Nadu, India – 631552
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Chen J, Wang M, Chen Y, Chen S, Xiao J, Fan X, Yang J, He B. A clinical study of inferior mesenteric artery typing in laparoscopic radical resections with left colonic artery preservation of rectal cancer. World J Surg Oncol 2022; 20:292. [PMID: 36089588 PMCID: PMC9465900 DOI: 10.1186/s12957-022-02762-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 09/05/2022] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVES An investigation of the effects of different types of the inferior mesenteric artery (IMA) on laparoscopic left colic artery (LCA) radical resection of rectal cancer was conducted. METHODS Clinical data were collected from 92 patients who underwent laparoscopic radical resection of rectal cancer with preservation of the LCA at Nantong University's Second Affiliated Hospital. All patients underwent full-abdominal dual-energy CT enhancement examination before surgery and 3D post-processing reconstruction of the IMA. Two radiologists with >3 years of experience in abdominal radiology jointly conducted the examination. A total of three types of IMA were identified among the patients: IMA type I (the LCA arising independently from the IMA), type II (LCA and sigmoid colon artery [SA] branching from a common trunk from IMA), and type III (LCA, SA, and superior rectal artery [SRA] branching from the IMA at the same point). The baseline data, pathological results, and intra-operative and post-operative indicators of the groups were analyzed. RESULTS The proportions of type I, type II, and type III IMA were 58.70% (54/92), 18.48% (17/92), and 22.82% (21/92), respectively. IMA typing was consistent with the preoperative CT evaluation results. The intra-operative blood loss of type III IMA patients [median (interquartile spacing), M (P25, P75): 52.00 (39.50, 68.50) ml] was higher than that of type I and II IMA patients [35.00 (24.00, 42.00) and 32.00 (25.50, 39.50) ml, respectively] (P<0.05). The incidence of anastomotic fistula in type III IMA patients (4 cases, 19.05%) was higher than that in non-type III IMA patients (1 case, 1.41%) (X2=6.679, P=0.010). The incidence of postoperative complications among the three types of IMA was not significantly different (P>0.05). CONCLUSIONS Among rectal cancer patients undergoing laparoscopic LCA preservation, type III IMA patients had more intraoperative bleeding and a higher incidence of postoperative anastomotic fistula. However, this did not increase the risk of overall postoperative complications.
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Affiliation(s)
- Jinghao Chen
- Department of Radiology, Affiliated Hospital 2 of Nantong University, No.6 Hai Er Xiang North Road, Nantong, 226001 Jiangsu Province China
- Department of Radiology, Affiliated Hospital of Nantong University, Nantong, 226006 Jiangsu Province China
| | - Meirong Wang
- Department of Radiology, Affiliated Hospital 2 of Nantong University, No.6 Hai Er Xiang North Road, Nantong, 226001 Jiangsu Province China
| | - Yuhao Chen
- Department of Radiology, Affiliated Hospital 2 of Nantong University, No.6 Hai Er Xiang North Road, Nantong, 226001 Jiangsu Province China
| | - Suying Chen
- Department of Radiology, Affiliated Hospital 2 of Nantong University, No.6 Hai Er Xiang North Road, Nantong, 226001 Jiangsu Province China
| | - Jing Xiao
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, 226019 Jiangsu Province China
| | - Xiaole Fan
- Department of Radiology, Affiliated Hospital 2 of Nantong University, No.6 Hai Er Xiang North Road, Nantong, 226001 Jiangsu Province China
| | - Jushun Yang
- Department of Radiology, Affiliated Hospital 2 of Nantong University, No.6 Hai Er Xiang North Road, Nantong, 226001 Jiangsu Province China
| | - Bosheng He
- Department of Radiology, Affiliated Hospital 2 of Nantong University, No.6 Hai Er Xiang North Road, Nantong, 226001 Jiangsu Province China
- Nantong Key Laboratory of Intelligent Medicine Innovation and Transformation, Nantong, 226001 Jiangsu China
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Luminal A Breast Cancer: How Feasible is Omitting Axillary Dissection Without Neoadjuvant Therapy. Breast J 2022; 2022:8284814. [PMID: 35974878 PMCID: PMC9356774 DOI: 10.1155/2022/8284814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 04/21/2022] [Accepted: 07/05/2022] [Indexed: 11/17/2022]
Abstract
Background. Luminal A breast cancer has a good prognosis and the criteria for adjuvant and neoadjuvant chemotherapy (NAC) are not clear. The aim of this study was to present our results of upfront surgery and long-term survival in luminal A tumors as well as the rates of protection from axillary dissection. Material and Methods. 271 Luminal A breast cancer patients who had operated at our center were evaluated retrospectively. In patients with 2 or less sentinel lymph node (SLN) positivity who did not receive neoadjuvant therapy and underwent breast-conserving surgery, axillary lymph node dissection was omitted (OAD). Axillary lymph node dissection (ALND) was performed in patients with positive SLN who did not meet these criteria (axillary dissection after sentinel/ADAS). Results. While Sentinel Lymph Node Biopsy (SLNB) was performed in 212 (77.9%) patients, SLNB + Axillary Dissection (AD) was performed in 58 (21.3%), and direct axillary dissection was performed in 1 (0.8%) patient. OAD was applied to 18 (23.6%) of the positive patients. Discussion/Conclusions. ALND rates are still strikingly high in luminal A breast cancer treatment, despite the disease’s milder clinical course. In order to avoid complications of axillary dissection, patients should be considered for NAC as much as possible. Novel neoadjuvant or other therapy options are also required.
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Umarani PJ, Rudresh KB, Smitha T, Rajaram P. Assessment of epidermal growth factor receptor in histological, clinical and pathological staging of oral squamous cell carcinoma. J Oral Maxillofac Pathol 2022; 26:362-365. [PMID: 36588836 PMCID: PMC9802500 DOI: 10.4103/jomfp.jomfp_149_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 06/03/2022] [Accepted: 07/06/2022] [Indexed: 01/03/2023] Open
Abstract
Background Oral squamous cell carcinoma is an invasive epithelial neoplasm with varying degrees of squamous differentiation that arises from the following anatomic sites: the oral cavity, particularly oral soft tissues including the gingival and alveolar mucosa, floor of the mouth, tongue, soft and hard palate, tonsils and oropharynx. In normal epithelium EGFR is localized to basal cell layer, while its expression beyond basal localization in cancerous tissue suggest that correlation of EGFR and tumor progression might exist. The present study aimed to assess epidermal growth factor receptor in histological, clinical and pathological staging of oral squamous cell carcinoma. Materials and Methods The current study was performed on subject with confirmed histological diagnosis of oral squamous cell carcinoma of age group between 35 and 70 years reported to Kempe-Gowda Institute of Medical Science and Hospital, Department of Oral and Maxillofacial Surgery, Vokkaligara Sangha Dental College and Hospital Bangalore and KIDWAI Memorial Institute of Oncology, Bangalore between December 2019 and March 2021. Total of 30 subjects included in the study of age group between 35 and 70 years. In the selected subject for the study, tumor was resected and preserved in 10% formalin, which was sent to department of pathology for analysis and PTNM was recorded. Immunohistochemical evaluation of EGFR was done. Total score of EGFR of each subject was co-related with pathological prognostic factor. Results Correlation of EGFR with adjuvant therapy and histological grading, P values were 0.001 and 0.005, respectively. The obtained results were tabulated statistically using Chi square test and significance was set at P < 0.05. Conclusion A preventive approach and assessment of EGFR in early stage of SCC provide better results. Subjects with higher EGFR value have poor prognosis and have to undergo postsurgical adjuvant therapy for long term-survival.
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Affiliation(s)
- Priyanka Jagadish Umarani
- Department of Oral and Maxillofacial Pathology, Vokkaligara Sangha Dental College, Bengaluru, Karnataka, India
| | - K B Rudresh
- Department of Oral and Maxillofacial Pathology, Vokkaligara Sangha Dental College, Bengaluru, Karnataka, India
| | - T Smitha
- Department of Oral and Maxillofacial Pathology, Vokkaligara Sangha Dental College, Bengaluru, Karnataka, India
| | - Prashanth Rajaram
- Department of Oral and Maxillofacial Pathology, Vokkaligara Sangha Dental College, Bengaluru, Karnataka, India
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Yazdanirad S, Pourtaghi G, Raei M, Ghasemi M. Development and validation of a tool for the comprehensive risk assessment of musculoskeletal disorders (CRAMUD) among employees of a steel industry. THEORETICAL ISSUES IN ERGONOMICS SCIENCE 2022. [DOI: 10.1080/1463922x.2022.2086643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Saeid Yazdanirad
- School of Health, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Gholamhossein Pourtaghi
- Health Research Center, Lifestyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mehdi Raei
- Health Research Center, Lifestyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mohammad Ghasemi
- Health Research Center, Lifestyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
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Al Khader A, Fararjeh AFS, Kaddumi EG, Al-Saghbini M. Significance of fibulin-3 expression in bladder cancer: a tissue microarray-based immunohistochemical study. World J Surg Oncol 2022; 20:133. [PMID: 35473807 PMCID: PMC9040230 DOI: 10.1186/s12957-022-02597-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 04/16/2022] [Indexed: 12/25/2022] Open
Abstract
Background Predicting the behavior of bladder cancer by easy noninvasive methods and with less cost is needed. Fibulin-3 (EFEMP1), a glycoprotein of the extracellular matrix that is encoded by the gene EFEMP1, has been nominated as one of the potential mediators of muscle invasion in bladder cancer. Methods In this tissue microarray-based immunohistochemical study, fibulin-3 level of expression was evaluated using a semiquantitative scoring system and was correlated with patient’s age and sex and tumor grade and stage. Results A total of 160 urothelial carcinoma cases were analyzed. The age of the patients ranged from 25 to 91 years (mean, 60.15; SD, 11.60). Fibulin-3 was significantly associated with muscle invasion and overall tumor stage (p = 0.033 and 0.02, respectively). Fibulin-3 expression was nonsignificantly associated with tumor grade (p = 0.092) Conclusions We found that the expression of fibulin-3 is significantly associated with muscle invasion in urinary bladder urothelial carcinoma. However, the prognostic role of fibulin-3 needs further investigations.
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Affiliation(s)
- Ali Al Khader
- Department of Pathology and Forensic Medicine, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan.
| | - Abdul Fattah S Fararjeh
- Department of Medical Laboratory Analysis, Faculty of Science, Al-Balqa Applied University, Al-Salt, Jordan
| | - Ezidin G Kaddumi
- Department of Basic Medical Sciences, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan
| | - Mohamad Al-Saghbini
- Department of Pathology and Forensic Medicine, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan
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Li W, Liu Y, Liu W, Tang ZR, Dong S, Li W, Zhang K, Xu C, Hu Z, Wang H, Lei Z, Liu Q, Guo C, Yin C. Machine Learning-Based Prediction of Lymph Node Metastasis Among Osteosarcoma Patients. Front Oncol 2022; 12:797103. [PMID: 35515104 PMCID: PMC9067126 DOI: 10.3389/fonc.2022.797103] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 03/15/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Regional lymph node metastasis is a contributor for poor prognosis in osteosarcoma. However, studies on risk factors for predicting regional lymph node metastasis in osteosarcoma are scarce. This study aimed to develop and validate a model based on machine learning (ML) algorithms. METHODS A total of 1201 patients, with 1094 cases from the surveillance epidemiology and end results (SEER) (the training set) and 107 cases (the external validation set) admitted from four medical centers in China, was included in this study. Independent risk factors for the risk of lymph node metastasis were screened by the multifactorial logistic regression models. Six ML algorithms, including the logistic regression (LR), the gradient boosting machine (GBM), the extreme gradient boosting (XGBoost), the random forest (RF), the decision tree (DT), and the multilayer perceptron (MLP), were used to evaluate the risk of lymph node metastasis. The prediction model was developed based on the bestpredictive performance of ML algorithm and the performance of the model was evaluatedby the area under curve (AUC), prediction accuracy, sensitivity and specificity. A homemade online calculator was capable of estimating the probability of lymph node metastasis in individuals. RESULTS Of all included patients, 9.41% (113/1201) patients developed regional lymph node metastasis. ML prediction models were developed based on nine variables: age, tumor (T) stage, metastasis (M) stage, laterality, surgery, radiation, chemotherapy, bone metastases, and lung metastases. In multivariate logistic regression analysis, T and M stage, surgery, and chemotherapy were significantly associated with lymph node metastasis. In the six ML algorithms, XGB had the highest AUC (0.882) and was utilized to develop as prediction model. A homemade online calculator was capable of estimating the probability of CLNM in individuals. CONCLUSIONS T and M stage, surgery and Chemotherapy are independent risk factors for predicting lymph node metastasis among osteosarcoma patients. XGB algorithm has the best predictive performance, and the online risk calculator can help clinicians to identify the risk probability of lymph node metastasis among osteosarcoma patients.
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Affiliation(s)
- Wenle Li
- Department of Orthopedics, Xianyang Central Hospital, Xianyang, China
- Clinical Medical Research Center, Xianyang Central Hospital, Xianyang, China
| | - Yafeng Liu
- School of Medicine, Anhui University of Science and Technology, Huainan, China
- Affiliated Cancer Hospital, Anhui University of Science and Technology, Huainan, China
| | - Wencai Liu
- Department of Orthopaedic Surgery, the First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zhi-Ri Tang
- School of Physics and Technology, Wuhan University, Wuhan, China
| | - Shengtao Dong
- Department of Spine Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Wanying Li
- Clinical Medical Research Center, Xianyang Central Hospital, Xianyang, China
| | - Kai Zhang
- Department of Orthopedics, Xianyang Central Hospital, Xianyang, China
- Clinical Medical Research Center, Xianyang Central Hospital, Xianyang, China
| | - Chan Xu
- Clinical Medical Research Center, Xianyang Central Hospital, Xianyang, China
| | - Zhaohui Hu
- Department of Spine Surgery, Liuzhou People’s Hospital, Liuzhou, China
| | - Haosheng Wang
- Department of Orthopaedics, The Second Hospital of Jilin University, Changchun, China
| | - Zhi Lei
- Chronic Disease Division, Luzhou Center for Dcontrol and Prevention, Luzhou, China
| | - Qiang Liu
- Department of Orthopedics, Xianyang Central Hospital, Xianyang, China
| | - Chunxue Guo
- Biostatistics Department, Hengpu Yinuo (Beijing) Technology Co., Ltd, Beijing, China
| | - Chengliang Yin
- Faculty of Medicine, Macau University of Science and Technology, Macau, Macau SAR, China
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Hsa-miR-181a-5p, hsa-miR-182-5p, and hsa-miR-26a-5p as potential biomarkers for BCR-ABL1 among adult chronic myeloid leukemia treated with tyrosine kinase inhibitors at the molecular response. BMC Cancer 2022; 22:332. [PMID: 35346116 PMCID: PMC8962036 DOI: 10.1186/s12885-022-09396-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 03/09/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Tyrosine kinase inhibitors (TKIs) as first-line therapy for Chronic Myeloid Leukemia (CML) show a high success rate. However, a low number of patients with long-term treatment-free remission (TFR) were observed. Molecular relapse after imatinib discontinuation occurred at 50% at 24 months, with 80% occurrence within the first 6 months. One of the reasons for relapse is untimely TKIs discontinuation caused by large errors from estimates at very low-level or undetectable disease, thus warranting new biomarkers for CML. METHODS Next Generation Sequencing (NGS) was used to identify microRNAs (miRNAs) at the molecular response in CML adult patients receiving TKIs treatment. A total of 86 samples were collected, 30 from CML patients responsive and 28 from non-responsive to imatinib therapy, and 28 from blood donors. NGS was conducted whereby 18 miRNAs were selected and validated by real-time RT-qPCR in triplicate. RESULTS Hsa-miR-181a-5p was expressed significantly (p-value< 0.05) with 2.14 and 2.33-fold down-regulation in both patient groups, respectively meanwhile hsa-miR-182-5p and hsa-miR-26a-5p were significant only in the non-responsive group with 2.08 and 2.39 fold up-regulation. The down-regulation was consistent with decreased amounts of BCR-ABL1 in patients taking TKIs regardless of molecular responses. The up-regulation was consistent with the substantial presence of BCR-ABL1 in CML patients treated with TKIs at the molecular response. CONCLUSIONS Therefore, these miRNAs have potential as new therapeutic biomarkers for BCR-ABL1 status in adult CML patients treated with TKIs at molecular responses. These could improve current approaches and require further analysis to look for targets of these miRNAs in CML.
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Harris CR, McKinley ET, Roland JT, Liu Q, Shrubsole MJ, Lau KS, Coffey RJ, Wrobel J, Vandekar SN. Quantifying and correcting slide-to-slide variation in multiplexed immunofluorescence images. Bioinformatics 2022; 38:1700-1707. [PMID: 34983062 PMCID: PMC8896603 DOI: 10.1093/bioinformatics/btab877] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 12/06/2021] [Accepted: 12/31/2021] [Indexed: 02/04/2023] Open
Abstract
MOTIVATION Multiplexed imaging is a nascent single-cell assay with a complex data structure susceptible to technical variability that disrupts inference. These in situ methods are valuable in understanding cell-cell interactions, but few standardized processing steps or normalization techniques of multiplexed imaging data are available. RESULTS We implement and compare data transformations and normalization algorithms in multiplexed imaging data. Our methods adapt the ComBat and functional data registration methods to remove slide effects in this domain, and we present an evaluation framework to compare the proposed approaches. We present clear slide-to-slide variation in the raw, unadjusted data and show that many of the proposed normalization methods reduce this variation while preserving and improving the biological signal. Furthermore, we find that dividing multiplexed imaging data by its slide mean, and the functional data registration methods, perform the best under our proposed evaluation framework. In summary, this approach provides a foundation for better data quality and evaluation criteria in multiplexed imaging. AVAILABILITY AND IMPLEMENTATION Source code is provided at: https://github.com/statimagcoll/MultiplexedNormalization and an R package to implement these methods is available here: https://github.com/ColemanRHarris/mxnorm. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
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Affiliation(s)
- Coleman R Harris
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37203, USA
| | - Eliot T McKinley
- Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
| | - Joseph T Roland
- Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
| | - Qi Liu
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37203, USA
- Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Martha J Shrubsole
- Division of Epidemiology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Ken S Lau
- Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
| | - Robert J Coffey
- Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Julia Wrobel
- Department of Biostatistics & Informatics, Colorado School of Public Health, Aurora, CO 80045, USA
| | - Simon N Vandekar
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37203, USA
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Banthia P, Gambhir L, Sharma A, Daga D, Kapoor N, Chaudhary R, Sharma G. Nano to rescue: repository of nanocarriers for targeted drug delivery to curb breast cancer. 3 Biotech 2022; 12:70. [PMID: 35223356 PMCID: PMC8841383 DOI: 10.1007/s13205-022-03121-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 01/16/2022] [Indexed: 12/17/2022] Open
Abstract
Breast cancer is a heterogeneous disease with different intrinsic subtypes. The conventional treatment of surgical resection, chemotherapy, immunotherapy and radiotherapy has not shown significant improvement in the survival rate of breast cancer patients. The therapeutics used cause bystander toxicities deteriorating healthy tissues. The breakthroughs of nanotechnology have been a promising feat in selective targeting of tumor site thus increasing the therapeutic gain. By the application of nanoenabled carriers, nanomedicines ensure targeted delivery, stability, enhanced cellular uptake, biocompatibility and higher apoptotic efficacy. The present review focuses on breakthrough of nanoscale intervention in targeted drug delivery as novel class of therapeutics. Nanoenabled carriers like polymeric and metallic nanoparticles, dendrimers, quantum dots, liposomes, solid lipid nanoparticles, carbon nanotubes, drug-antibody conjugates and exosomes revolutionized the targeted therapeutic delivery approach. These nanoassemblies have shown additional effect of improving the solubility of drugs such as paclitaxel, reducing the dose and toxicity. The present review provides an insight on the different drug conjugates employed/investigated to curb breast cancer using nanocarrier mediated targeted drug delivery. However, identification of appropriate biomarkers to target, clearer insight of the biological processes, batch uniformity, reproducibility, nanomaterial toxicity and stabilities are the hurdles faced by nanodrugs. The potential of nano-therapeutics delivery necessitates the agglomerated efforts of research community to bridge the route of nanodrugs for scale-up, commercialization and clinical applications.
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Affiliation(s)
- Poonam Banthia
- School of Applied Sciences, Suresh Gyan Vihar University, Jaipur, Rajasthan India
| | - Lokesh Gambhir
- School of Applied Sciences, Suresh Gyan Vihar University, Jaipur, Rajasthan India
| | - Asha Sharma
- Department of Zoology, Swargiya P. N. K. S. Govt. PG College, Dausa, Rajasthan India
| | - Dhiraj Daga
- Department of Radiation Oncology, JLN Medical College, Ajmer, Rajasthan India
| | - Neha Kapoor
- School of Applied Sciences, Suresh Gyan Vihar University, Jaipur, Rajasthan India
| | - Rishabh Chaudhary
- Department of Emergency Medicine, Institute of Bioelectronic Medicine, Feinstein Institute of Medical Research, Northwell Health, New Hyde Park, NY USA
| | - Gaurav Sharma
- School of Applied Sciences, Suresh Gyan Vihar University, Jaipur, Rajasthan India
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A Complex Radiomic Signature in Luminal Breast Cancer from a Weighted Statistical Framework: A Pilot Study. Diagnostics (Basel) 2022; 12:diagnostics12020499. [PMID: 35204589 PMCID: PMC8871349 DOI: 10.3390/diagnostics12020499] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 02/08/2022] [Accepted: 02/12/2022] [Indexed: 01/27/2023] Open
Abstract
Radiomics is rapidly advancing in precision diagnostics and cancer treatment. However, there are several challenges that need to be addressed before translation to clinical use. This study presents an ad-hoc weighted statistical framework to explore radiomic biomarkers for a better characterization of the radiogenomic phenotypes in breast cancer. Thirty-six female patients with breast cancer were enrolled in this study. Radiomic features were extracted from MRI and PET imaging techniques for malignant and healthy lesions in each patient. To reduce within-subject bias, the ratio of radiomic features extracted from both lesions was calculated for each patient. Radiomic features were further normalized, comparing the z-score, quantile, and whitening normalization methods to reduce between-subjects bias. After feature reduction by Spearman’s correlation, a methodological approach based on a principal component analysis (PCA) was applied. The results were compared and validated on twenty-seven patients to investigate the tumor grade, Ki-67 index, and molecular cancer subtypes using classification methods (LogitBoost, random forest, and linear discriminant analysis). The classification techniques achieved high area-under-the-curve values with one PC that was calculated by normalizing the radiomic features via the quantile method. This pilot study helped us to establish a robust framework of analysis to generate a combined radiomic signature, which may lead to more precise breast cancer prognosis.
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Zhang J, Dong Y, Shi Z, He H, Chen J, Zhang S, Wu W, Zhang Q, Han C, Hao L. P3H4 and PLOD1 expression associates with poor prognosis in bladder cancer. Clin Transl Oncol 2022; 24:1524-1532. [PMID: 35149972 DOI: 10.1007/s12094-022-02791-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 01/21/2022] [Indexed: 12/24/2022]
Abstract
PURPOSE The prolyl 3-hydroxylase family member 4 gene (P3H4) is involved in the development of human cancers. The association of P3H4 with bladder cancer (BC) prognosis is unclear. This study aimed to analyze the association of P3H4 with BC prognosis. METHODS RNA-Seq data were downloaded from The Cancer Genome Atlas project and BC microarray datasets (GSE13507, GSE31684, and GSE32548) were downloaded from the Gene Expression Omnibus database. We analyzed the differences in P3H4 expression levels between BC tumors and non-tumor tissues and between samples with different clinical information. The association of P3H4 and P3H4-related genes with BC prognosis and the possibility of using P3H4 expression as a prognostic biomarker in BC patients were also analyzed. RevMan was used to perform the meta-analysis. RESULTS P3H4 was upregulated in BC tissues compared with the adjacent non-tumor tissues (p = 4.06e-08). Univariate Cox regression analysis and meta-analysis showed that high P3H4 expression level contributed to a poor BC prognosis (Hazard ratio, HR = 1.348, 95% CI 1.140-1.594, p = 4.89e-04; meta-analysis: HR = 1.45, 95% CI 1.10-1.91; p = 9.00e-03). Among the genes related to P3H4, the PLOD1 gene was closely associated with P3H4 expression (r = 0.620, p = 2.49e-44). Also, a meta-analysis showed that PLOD1 expression was associated with a poor prognosis in BC patients (HR = 1.77, 95% CI 1.31-2.38; p = 2.00e-04). CONCLUSIONS The P3H4 and PLOD1 genes might be used as reliable prognostic biomarkers for BC.
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Affiliation(s)
- Junjie Zhang
- Medical College of Soochow University, Suzhou, 215123, Jiangsu, China.,Department of Urology, Xuzhou Central Hospital, 199 Jiefang South Road, Xuzhou, 221009, Jiangsu, China
| | - Yang Dong
- Medical College of Soochow University, Suzhou, 215123, Jiangsu, China.,Department of Urology, Xuzhou Central Hospital, 199 Jiefang South Road, Xuzhou, 221009, Jiangsu, China
| | - Zhenduo Shi
- Department of Urology, Xuzhou Central Hospital, 199 Jiefang South Road, Xuzhou, 221009, Jiangsu, China
| | - Houguang He
- Department of Urology, Xuzhou Central Hospital, 199 Jiefang South Road, Xuzhou, 221009, Jiangsu, China
| | - Jiangang Chen
- Medical College of Soochow University, Suzhou, 215123, Jiangsu, China
| | - Shaoqi Zhang
- Medical College of Soochow University, Suzhou, 215123, Jiangsu, China
| | - Wei Wu
- Medical College of Soochow University, Suzhou, 215123, Jiangsu, China
| | - Qianjin Zhang
- Medical College of Soochow University, Suzhou, 215123, Jiangsu, China
| | - Conghui Han
- Medical College of Soochow University, Suzhou, 215123, Jiangsu, China.,Department of Urology, Xuzhou Central Hospital, 199 Jiefang South Road, Xuzhou, 221009, Jiangsu, China
| | - Lin Hao
- Medical College of Soochow University, Suzhou, 215123, Jiangsu, China. .,Department of Urology, Xuzhou Central Hospital, 199 Jiefang South Road, Xuzhou, 221009, Jiangsu, China.
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Bacha RH, Jabir YN, Asebot AG, Liga AD. Risk Factors Affecting Survival Time of Breast Cancer Patients: The case of Southwest Ethiopia. J Res Health Sci 2021; 21:e00532. [PMID: 36511228 PMCID: PMC8957664 DOI: 10.34172/jrhs.2021.65] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 09/27/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Breast cancer is one of the non-communicable diseases and the main origin of the loss of life in the world. In Ethiopia, breast cancer is the second common cancer health problem for women. The main objective of this study was to identify the potential risk factors affecting the survival time of breast cancer patients in Southwest Ethiopia. STUDY DESIGN A retrospective study design. METHODS The data were taken from the patients' medical records that registered from January 1, 2015, to January 31, 2020. A retrospective study design was used in this study. Different shared frailty survival models were employed to analyze the dataset. RESULTS Out of 642 recorded breast cancer patients, 447(69.6%) cases died during the study period, and 195 (30.4%) patients lost follow-up for unknown reasons. The median time to death for breast cancer patients was 10 months, and hospitals were used as a cluster effect. The result revealed that women with no smoking habit had about 3.35 times higher survival time than patients who had a smoking habit, and as breast cancer patients age increased, the survival time decreased by 0.99. Moreover, breast cancer patients in rural areas had about 0.14 times lower survival time, compared to breast cancer patients who were urban residents. CONCLUSIONS Age, place of residence, treatment taken, stage, histologic grade, tumor size, oral contraceptives, and smoking habits led to a shorter survival time. To reduce the burden of breast cancer, awareness should be given to the community.
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Affiliation(s)
- Reta Habtamu Bacha
- Department of Statistics, College of Natural Sciences, Jimma University, Jimma, Ethiopia
,Correspondence: Reta Habtamu Bacha (MSc) Tel: +25 1912237159 E-mail:
| | - Yasin Negash Jabir
- Department of Statistics, College of Natural Sciences, Jimma University, Jimma, Ethiopia
| | - Anberbir Girma Asebot
- Department of Obstetrics and Gynecology, Institute of Health Sciences, Jimma University, Jimma, Ethiopia
| | - Abebe Debu Liga
- Department of Statistics, College of Natural and Computational Sciences, Wolkite University, Wolkite, Ethiopia
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Predictive modelling of level IIb lymph node metastasis in oral squamous cell carcinoma. Sci Rep 2021; 11:17562. [PMID: 34475441 PMCID: PMC8413325 DOI: 10.1038/s41598-021-96827-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 08/12/2021] [Indexed: 02/07/2023] Open
Abstract
The aim of the present study was to examine the conditions, characteristics, and risk factors of level IIb lymph node metastases in oral squamous cell carcinoma and to formulate surgical criteria for level IIb lymph node dissection. We analyzed clinical and pathological records for 541 oral squamous carcinoma patients in relation to level IIb metastasis. Univariate and multivariate analyses were performed to detect risk factors for level IIb lymph node metastasis; a predictive model was built based on multivariate analysis and tested in a validation group. Univariate and multivariate analyses using the training group indicated that level IIa metastasis and Lymphovascular permeation (LVP) were two independent risk factors for level IIb lymph node metastasis. This model was built and tested in a validation group, the area under the curve being 0.697 (P < .0.001). The model's sensitivity was 66.7% and specificity was 77.4%. Nomogram incorporating validated variables was developed for level IIb metastasis prediction. Expected survival probabilites were analysed to specify significance of model's variable on patients' overall survival and recurrence. Level IIb dissection should be performed in patients with level IIa metastasis and LVP. However, thorough consideration of the oncologic safety of omitting level IIb dissection is compulsory.
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Burks HE, Matossian MD, Rhodes LV, Phamduy T, Elliott S, Buechlein A, Rusch DB, Miller DFB, Nephew KP, Chrisey D, Collins-Burow BM, Burow ME. ZEB2 regulates endocrine therapy sensitivity and metastasis in luminal a breast cancer cells through a non-canonical mechanism. Breast Cancer Res Treat 2021; 189:25-37. [PMID: 34231077 DOI: 10.1007/s10549-021-06256-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 05/04/2021] [Indexed: 01/23/2023]
Abstract
PURPOSE The transcription factors ZEB1 and ZEB2 mediate epithelial-to-mesenchymal transition (EMT) and metastatic progression in numerous malignancies including breast cancer. ZEB1 and ZEB2 drive EMT through transcriptional repression of cell-cell junction proteins and members of the tumor suppressive miR200 family. However, in estrogen receptor positive (ER +) breast cancer, the role of ZEB2 as an independent driver of metastasis has not been fully investigated. METHODS In the current study, we induced exogenous expression of ZEB2 in ER + MCF-7 and ZR-75-1 breast cancer cell lines and examined EMT gene expression and metastasis using dose-response qRT-PCR, transwell migration assays, proliferation assays with immunofluorescence of Ki-67 staining. We used RNA sequencing to identify pathways and genes affected by ZEB2 overexpression. Finally, we treated ZEB2-overexpressing cells with 17β-estradiol (E2) or ICI 182,780 to evaluate how ZEB2 affects estrogen response. RESULTS Contrary to expectation, we found that ZEB2 did not increase canonical epithelial nor decrease mesenchymal gene expressions. Furthermore, ZEB2 overexpression did not promote a mesenchymal cell morphology. However, ZEB1 and ZEB2 protein expression induced significant migration of MCF-7 and ZR-75-1 breast cancer cells in vitro and MCF-7 xenograft metastasis in vivo. Transcriptomic (RNA sequencing) pathway analysis revealed alterations in estrogen signaling regulators and pathways, suggesting a role for ZEB2 in endocrine sensitivity in luminal A breast cancer. Expression of ZEB2 was negatively correlated with estrogen receptor complex genes in luminal A patient tumors. Furthermore, treatment with 17β-estradiol (E2) or the estrogen receptor antagonist ICI 182,780 had no effect on growth of ZEB2-overexpressing cells. CONCLUSION ZEB2 is a multi-functional regulator of drug sensitivity, cell migration, and metastasis in ER + breast cancer and functions through non-canonical mechanisms.
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Affiliation(s)
- Hope E Burks
- Department of Medicine, Section of Hematology & Medical Oncology, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA.,Tulane Cancer Center, New Orleans, LA, 70112, USA
| | - Margarite D Matossian
- Department of Medicine, Section of Hematology & Medical Oncology, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA.,Tulane Cancer Center, New Orleans, LA, 70112, USA
| | | | - Theresa Phamduy
- Department of Physics, Tulane University, New Orleans, LA, 70112, USA
| | - Steven Elliott
- Department of Medicine, Section of Hematology & Medical Oncology, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA.,Tulane Cancer Center, New Orleans, LA, 70112, USA
| | - Aaron Buechlein
- Center of Genomics and Bioinformatics, Indiana University, Bloomington, IN, 47405, USA
| | - Douglas B Rusch
- Center of Genomics and Bioinformatics, Indiana University, Bloomington, IN, 47405, USA
| | - David F B Miller
- Center of Genomics and Bioinformatics, Indiana University, Bloomington, IN, 47405, USA.,Medical Sciences Program, Indiana University School of Medicine, Bloomington, IN, 47405, USA
| | - Kenneth P Nephew
- Medical Sciences Program, Indiana University School of Medicine, Bloomington, IN, 47405, USA
| | - Douglas Chrisey
- Department of Physics, Tulane University, New Orleans, LA, 70112, USA
| | - Bridgette M Collins-Burow
- Department of Medicine, Section of Hematology & Medical Oncology, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA.,Tulane Cancer Center, New Orleans, LA, 70112, USA
| | - Matthew E Burow
- Department of Medicine, Section of Hematology & Medical Oncology, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA. .,Tulane Cancer Center, New Orleans, LA, 70112, USA.
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Hashmi AA, Riaz R, Zia S, Shahid H, Malik UA, Khan R, Irfan M, Shamail F, Zia F, Asif MG. Impact of Histological Type and Grade on the Diagnostic Accuracy of Intraoperative Frozen Section for Detecting Breast Cancer Metastasis to Axillary Sentinel Lymph Nodes. Cureus 2021; 13:e16146. [PMID: 34354885 PMCID: PMC8328395 DOI: 10.7759/cureus.16146] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/03/2021] [Indexed: 01/10/2023] Open
Abstract
Introduction Intraoperative sentinel lymph node (SLN) evaluation is the standard of care in patients with clinically node-negative breast cancer. The most common histological subtype of breast carcinoma is invasive ductal carcinoma (IDC), followed by invasive lobular carcinoma (ILC). Alternatively, histological grades vary from grades G1 to G3. Therefore, in this study, we evaluated the diagnostic accuracy of frozen section (FS) for detecting breast cancer metastasis to SLNs with respect to histological subtypes and grades. Methods A retrospective observational study was conducted in the Department of Histopathology at Liaquat National Hospital and Medical College, Pakistan, from January 2013 till December 2020, over a duration of eight years. A total of 540 cases of primary breast cancer, undergoing upfront breast surgery were included in the study. Intraoperatively, SLNs were identified and sent for FS. After FS reporting, the remaining tissue was submitted for final (paraffin) section examination after formalin fixation, and results of FS and final (paraffin) sections were compared. Results The mean age of the patients included in the study was 52.05±12.42 years, and the median number of SLNs was three (ranging from one to 14). The overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of intraoperative FS were 88.2%, 100%, 100%, 92.5%, and 95.2%, respectively. The sensitivity of FS for IDC was 88.3%, whereas it was 85.7% for ILC. Alternatively, the sensitivity of FS for grade G1, G2, and G3 tumors was 78.3%, 91.5%, and 90.2%, respectively. The false-negative rate for grade G1 tumors was 21.7%, which was higher than G2 and G3 tumors (8.5% and 9.8%, respectively). Similarly, the false-negative rate for cases where the number of SLNs was more than three was only 5.4%, which was lower than cases with a single and two to three SLNs sent on FS (23.1 and 14.7%, respectively). Conclusion The sensitivity of intraoperative FS for detecting ILC metastasis to axillary SLNs was not substantially different from IDC; however, histological grade affects the sensitivity of FS diagnosis, with lower-grade tumors having low sensitivity. Moreover, increasing the number of SLNs sent intraoperatively on FS improves the sensitivity of FS for detecting breast cancer metastasis to axillary SLNs.
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Affiliation(s)
- Atif A Hashmi
- Pathology, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Rubina Riaz
- Pathology, Fazaia Medical College, Air University, Islamabad, PAK
| | - Shamail Zia
- Pathology, Ziauddin University, Karachi, PAK
| | - Hiba Shahid
- Internal Medicine, Liaquat National Hospital and Medical College, Karachi, PAK
| | | | - Rabeet Khan
- Internal Medicine, Buckinghamshire Healthcare NHS Trust, Aylesbury, GBR
| | - Muhammad Irfan
- Statistics, Liaquat National Hospital and Medical College, Karachi, PAK
| | | | - Fazail Zia
- Pathology, Jinnah Sindh Medical University, Karachi, PAK
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Islam S, Kitagawa T, Baron B, Abiko Y, Chiba I, Kuramitsu Y. ITGA2, LAMB3, and LAMC2 may be the potential therapeutic targets in pancreatic ductal adenocarcinoma: an integrated bioinformatics analysis. Sci Rep 2021; 11:10563. [PMID: 34007003 PMCID: PMC8131351 DOI: 10.1038/s41598-021-90077-x] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 05/05/2021] [Indexed: 02/07/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer with an abysmal prognosis rate over the last few decades. Early diagnosis and prevention could effectively combat this malignancy. Therefore, it is crucial to discover potential biomarkers to identify asymptomatic premalignant or early malignant tumors of PDAC. Gene expression analysis is a powerful technique to identify candidate biomarkers involved in disease progression. In the present study, five independent gene expression datasets, including 321 PDAC tissues and 208 adjacent non-cancerous tissue samples, were subjected to statistical and bioinformatics analysis. A total of 20 differentially expressed genes (DEGs) were identified in PDAC tissues compared to non-cancerous tissue samples. Gene ontology and pathway enrichment analysis showed that DEGs were mainly enriched in extracellular matrix (ECM), cell adhesion, ECM-receptor interaction, and focal adhesion signaling. The protein-protein interaction network was constructed, and the hub genes were evaluated. Collagen type XII alpha 1 chain (COL12A1), fibronectin 1 (FN1), integrin subunit alpha 2 (ITGA2), laminin subunit beta 3 (LAMB3), laminin subunit gamma 2 (LAMC2), thrombospondin 2 (THBS2), and versican (VCAN) were identified as hub genes. The correlation analysis revealed that identified hub genes were significantly interconnected. Wherein COL12A1, FN1, ITGA2, LAMB3, LAMC2, and THBS2 were significantly associated with PDAC pathological stages. The Kaplan-Meier survival plots revealed that ITGA2, LAMB3, and LAMC2 expression were inversely correlated with a prolonged patient survival period. Furthermore, the Human Protein Atlas database was used to validate the expression and cellular origins of hub genes encoded proteins. The protein expression of hub genes was higher in pancreatic cancer tissue than in normal pancreatic tissue samples, wherein ITGA2, LAMB3, and LAMC2 were exclusively expressed in pancreatic cancer cells. Pancreatic cancer cell-specific expression of these three proteins may play pleiotropic roles in cancer progression. Our results collectively suggest that ITGA2, LAMB3, and LAMC2 could provide deep insights into pancreatic carcinogenesis molecular mechanisms and provide attractive therapeutic targets.
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Affiliation(s)
- Shajedul Islam
- Advanced Research Promotion Center, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan
| | - Takao Kitagawa
- Advanced Research Promotion Center, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan
| | - Byron Baron
- Centre for Molecular Medicine and Biobanking, University of Malta, Msida, MSD 2080, Malta
| | - Yoshihiro Abiko
- Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan
| | - Itsuo Chiba
- Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan
| | - Yasuhiro Kuramitsu
- Advanced Research Promotion Center, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
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Balmaganbetova FK, Amanzholkyzy A, Nurgaliyeva RE, Kaldybayeva AT, Zhexenova AN. Comparative Analysis of Vaginal Microbiota in Women with Breast Cancer in Kazakhstan. Asian Pac J Cancer Prev 2021; 22:1313-1318. [PMID: 33906327 PMCID: PMC8325121 DOI: 10.31557/apjcp.2021.22.4.1313] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 04/22/2021] [Indexed: 12/02/2022] Open
Abstract
OBJECT The relevance of the article is that the breast cancer is a leading oncological disease in women in developed countries and has the highest mortality caused by malignant neoplasms in women. The purpose of the study is to evaluate vaginal microbiota in women with various breast cancer subtypes and compared groups. METHODS The study involved 278 women with breast cancer, of whom 174 were patients receiving combination therapy; the control group consisted of 104 patients who had had breast cancer 2-4 years ago. RESULTS It was found that despite a significant decrease in the total number of Lactobacillus spp., there were no statistically significant changes in the numbers of microorganisms in patients with different subtypes of breast cancer. According to the results of the comparative analysis, the representatives of obligate anaerobic flora Peptostreptococcus spp. prevailed in vaginal microbiota in luminal A and luminal B subtypes, and the representative of the facultative anaerobic organisms Staphylococcus spp. - in unfavourable outcomes in Her2/Neu+ and triple-negative subtypes. CONCLUSION The observed features of the vaginal microbiota in women with different subtypes of breast cancer require further studies for preventive purposes.
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Affiliation(s)
- Farida K. Balmaganbetova
- Department of Normal Physiology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Republic of Kazakhstan.
| | - Ainur Amanzholkyzy
- Department of Normal Physiology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Republic of Kazakhstan.
| | - Roza E. Nurgaliyeva
- Department of Normal Physiology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Republic of Kazakhstan.
| | - Aiman T. Kaldybayeva
- Department of Normal Physiology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Republic of Kazakhstan.
| | - Azhar N. Zhexenova
- Department of Phatophysiology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Republic of Kazakhstan.
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Hashmi AA, Zia S, Yaqeen SR, Ahmed O, Asghar IA, Islam S, Afzal A, Irfan M, Zia F, Ali J. Mucinous Breast Carcinoma: Clinicopathological Comparison With Invasive Ductal Carcinoma. Cureus 2021; 13:e13650. [PMID: 33824803 PMCID: PMC8012174 DOI: 10.7759/cureus.13650] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Introduction Invasive ductal carcinoma (IDC) is the most common histological subtype of breast cancer. Conversely, many special types of breast carcinoma were described with varying prognosis and hormone receptor status. Mucinous carcinoma (MC) is a rare special subtype of breast cancer, and only a few studies have evaluated the clinicopathological and hormone receptor profile of this type of breast cancer. Therefore, in this study, we compared the clinicopathological characteristics of MC with IDC in our population. Methods A retrospective observational study was conducted in the Department of Histopathology, Liaquat National Hospital and Medical College, from January 2013 till December 2020, for eight years. During this period, 38 cases of MC were diagnosed and 1268 cases of IDC were identified. All specimens were grossed according to standard protocols and representative sections were submitted from tumors, resection margins, and lymph nodes. Slides were examined by histopathologists to determine tumor type and grade. Immunohistochemical (IHC) stains were applied to evaluate estrogen receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth factor receptor 2 (HER2/neu) statuses. Results The mean age of the patients with MC was 56.47±13.90 years, and most of the patients were above 50 years of age. The mean tumor size was 34.89±19.70 mm. Most tumors were grade 1 (68.4%) with a low mean Ki67 index (15.21±14.06%). Axillary metastasis was present in 31.6% of cases and all of them were nodal (N)-stage N1. ER, PR, and HER2/neu positivity were noted in 94.7%, 78.9, and 10.5% cases, respectively. Compared with IDC, a significant association of MC was noted with age, Ki67 index, tumor (T)-stage, N-stage, and tumor grade. MC cases had a higher mean age than IDC cases. Comparative analysis revealed that MC had a lower frequency of axillary metastasis, a lower mean Ki67 index, and a lower tumor grade than IDC. About biomarker status, MC was noted to have a higher frequency of ER and PR expression, and a lower frequency of HER2/neu expression than IDC. Conclusion MC is a rare subtype of breast cancer. However, it is important to recognize this subtype of breast cancer as it is associated with a prognostically better pathological profile, such as lower tumor grade and Ki67 index, lower frequency of axillary metastasis, higher expression of ER and PR, and lower expression of HER2/neu.
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Affiliation(s)
- Atif A Hashmi
- Pathology, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Shamail Zia
- Pathology, Ziauddin University, Karachi, PAK
| | | | - Omer Ahmed
- Internal Medicine, Liaquat National Hospital and Medical College, Karachi, PAK
| | | | - Sabeeh Islam
- Internal Medicine, St. Vincent Health Center, Buffalo, USA.,Internal Medicine, Faisalabad Medical University, Faisalabad, PAK
| | - Anoshia Afzal
- Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, USA
| | - Muhammad Irfan
- Statistics, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Fazail Zia
- Pathology, Jinnah Sindh Medical University, Karachi, PAK
| | - Javaria Ali
- Pathology, Liaquat National Hospital and Medical College, Karachi, PAK
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Griess B, Klinkebiel D, Kueh A, Desler M, Cowan K, Fitzgerald M, Teoh-Fitzgerald M. Association ofSOD3 promoter DNA methylation with its down-regulation in breast carcinomas. Epigenetics 2020; 15:1325-1335. [PMID: 32508251 PMCID: PMC7678930 DOI: 10.1080/15592294.2020.1777666] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 04/29/2020] [Accepted: 05/11/2020] [Indexed: 12/29/2022] Open
Abstract
Superoxide dismutase 3 (SOD3) is a secreted antioxidant enzyme that regulates reactive oxygen species in the microenvironment. It is also a potential tumour suppressor gene that is significantly downregulated in breast cancer. We have previously shown that its mRNA expression is inversely correlated with relapse free survival in breast cancer patients. This study aimed to investigate the correlation of SOD3 promoter DNA methylation with its expression in different molecular subtypes of breast carcinoma. We found that SOD3 expression was significantly reduced in breast carcinoma samples compared to normal tissues with the lowest levels observed in Luminal B subtype. Pyrosequencing analysis showed significant increase in methylation levels in the SOD3 promoter region (-108 and -19 from the TSS) in tumours vs normal tissues (53.6% vs 25.2%). The highest degree of correlation between methylation and SOD3 expression levels was observed in Luminal B subtype (Spearman's R = -0.540, P < 0.00093). In this subtype, the -78 CpG position is the most significantly methylated site. The Spearman's coefficient analysis also indicated the most significant correlation of DNA methylation at this site with SOD3 gene expression levels in tumours vs. normal tissues (R = -0.5816, P < 6.9E-12). Moreover, copy number variation analysis of TCGA database revealed that the more aggressive Triple Negative and Her2+ subtypes had higher levels of SOD3 gene deletion. The predominantly down-regulated expression pattern of SOD3 and the various genetic and epigenetic deregulations of its expression suggest that loss of this antioxidant promotes an advantageous tumour-promoting microenvironment in breast cancer.
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Affiliation(s)
- Brandon Griess
- Department of Biochemistry and Molecular Biology, Fred and Pamela Buffett Cancer Center, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - David Klinkebiel
- Department of Biochemistry and Molecular Biology, Fred and Pamela Buffett Cancer Center, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Alice Kueh
- Eppley Institute for Cancer Research, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
| | - Michelle Desler
- Eppley Institute for Cancer Research, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
| | - Kenneth Cowan
- Eppley Institute for Cancer Research, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
| | - Matthew Fitzgerald
- College of Nursing, University of Nebraska Medical Center, Omaha, NE, USA
| | - Melissa Teoh-Fitzgerald
- Department of Biochemistry and Molecular Biology, Fred and Pamela Buffett Cancer Center, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
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