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Gupta SRR, Mittal P, Kundu B, Singh A, Singh IK. Silibinin: an inhibitor for a high-expressed BCL-2A1/BFL1 protein, linked with poor prognosis in breast cancer. J Biomol Struct Dyn 2023; 42:12122-12132. [PMID: 37837418 DOI: 10.1080/07391102.2023.2268176] [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: 03/14/2023] [Accepted: 09/29/2023] [Indexed: 10/16/2023]
Abstract
Breast cancer (BC) accounts for 30% of all diagnosed cases of cancer in women and remains a leading cause of cancer-related deaths among women worldwide. The current study looks for a protein from the anti-apoptotic/pro-survival BCL-2 family whose overexpression reduces survivability in BC patients and a potential inhibitor for the protein. We found BCL-2A1/BFL1 protein with high expression linked to low survivability in BC. The protein shows prognosis in 8 out of 29 categories, whereas no other family member manifests this property. Out of 7379 compounds, three small molecules (CHEMBL9509, CHEMBL2104550 and CHEMBL3545011) form an H-bond with BCL-2A1/BFL1 protein's unique residue Cys55. Of the three small molecules, we found CHEMBL9509 (Silibinin) to be a potent inhibitor. The compound forms a stable H-bond with the residue Cys55 with the lowest binding energy compared to the other two compounds. It remains stable in the BH3 binding region for more than 100 ns, whereas the other two detach from the region. Additionally, the compound is found to be better than Venetoclax and Nematoclax. We firmly believe in the compound CHEMBL9509 potency to halt BC's progression by inhibiting the BCL-2A1/BFL1 protein, increasing patients' survivability.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Shradheya R R Gupta
- Molecular Biology Research Laboratory, Department of Zoology, Deshbandhu College, University of Delhi, New Delhi, India
| | - Pooja Mittal
- Molecular Biology Research Laboratory, Department of Zoology, Deshbandhu College, University of Delhi, New Delhi, India
- Norris Comprehensive Cancer Center, Division of Medical Oncology, University of Southern California, Los Angeles, USA
| | - Bishwajit Kundu
- Kusuma School of Biological Science, Indian Institute of Technology Delhi, New Delhi, India
| | - Archana Singh
- Department of Plant Molecular Biology, University of Delhi (South Campus), New Delhi, India
| | - Indrakant K Singh
- Molecular Biology Research Laboratory, Department of Zoology, Deshbandhu College, University of Delhi, New Delhi, India
- Norris Comprehensive Cancer Center, Division of Medical Oncology, University of Southern California, Los Angeles, USA
- Institute of Eminence, Delhi School of Public Health, University of Delhi, Delhi, India
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2
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Selimovic D, Kharouf N, Carrouel F, Hassan SY, Flanagan TW, Hassan SL, Megahed M, Haikel Y, Santourlidis S, Hassan M. Induction of Antimicrobial Protein S100A15 Expression by Oral Microbial Pathogens Is Toll-like Receptors-Dependent Activation of c-Jun-N-Terminal Kinase (JNK), p38, and NF-κB Pathways. Int J Mol Sci 2023; 24:ijms24065348. [PMID: 36982421 PMCID: PMC10049289 DOI: 10.3390/ijms24065348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 03/07/2023] [Accepted: 03/08/2023] [Indexed: 03/16/2023] Open
Abstract
The antimicrobial protein S100A15 belongs to the S100 family, which is differentially expressed in a variety of normal and pathological tissues. Although the function of S100A15 protein has been discussed in several studies, its induction and regulation in oral mucosa, so far, are largely unknown. In this study, we demonstrate that S100A15 is induced by the stimulation of oral mucosa with gram− or gram+ bacterial pathogens, as well as with the purified membrane components, namely lipopolysaccharides (LPS) and lipoteichoic acid (LTA). The stimulation of the human gingival fibroblast (GF) and the human mouth epidermal carcinoma (KB) cell lines with either gram− or gram+ bacterial pathogens or their purified membrane components (LPS and LTA) results in the activation of NF-κB, apoptosis-regulating kinase1 (ASK1), and MAP kinase signaling pathways including, c-Jun N-terminal kinase (JNK) and p38 together with their physiological substrates AP-1 and ATF-2, respectively. Inhibition of S100A15 by antibodies-mediated Toll-like receptor 4 (TLR4) or Toll-like receptor 2 (TLR2) neutralization reveals the induction of S100A15 protein by LPS/gram− bacterial pathogens to be TLR4- dependent mechanism, whereas induction by LTA/gram+ bacterial pathogens to be TLR2- dependent mechanism. Pre-treatment of GF and KB cells with JNK (SP600125), p38 (SB-203580), or NF-κB (Bay11-7082) specific inhibitors further demonstrates the importance of JNK, p38 and NF-κB pathways in the regulation of gram−/gram+ bacterial pathogen-induced S100A15 expression. Our data provide evidence that S100A15 is induced in cancer and non-cancer oral mucosa-derived cell lines by gram−/gram+ bacterial pathogens and provide insight into the molecular mechanisms by which gram− and gram+ bacterial pathogens induce S100A15 expression in the oral mucosa.
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Affiliation(s)
- Denis Selimovic
- Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, France
- Department of Restorative Dentistry, Endodontology and Biomaterials, Faculty of Dentistry, University of Tours, 37000 Tours, France
| | - Naji Kharouf
- Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, France
- Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France
| | - Florence Carrouel
- Health, Systemic, Process, UR 4129 Research Unit, University Claude Bernard Lyon 1, University of Lyon, 69008 Lyon, France
| | - Sofie-Yasmin Hassan
- Department of Chemistry, Faculty of Science, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, Germany
| | - Thomas W. Flanagan
- Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA 70112, USA
| | - Sarah-Lilly Hassan
- Department of Chemistry, Faculty of Science, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, Germany
| | - Mosaad Megahed
- Clinic of Dermatology, University Hospital of Aachen, 52074 Aachen, Germany
| | - Youssef Haikel
- Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, France
- Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France
| | - Simeon Santourlidis
- Institute of Cell Therapeutics and Diagnostics, University Medical Center of Duesseldorf, 40225 Duesseldorf, Germany
| | - Mohamed Hassan
- Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, France
- Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France
- Research Laboratory of Surgery-Oncology, Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USA
- Correspondence: ; Tel.: +1-504-339-2671
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Ren Y, Chen B, Zhang M, Xu F. Comprehensive analysis of the prognosis of S100 family members and their relationship with tumor-infiltrating immune cells in human pancreatic adenocarcinoma. Medicine (Baltimore) 2023; 102:e32976. [PMID: 36827067 PMCID: PMC11309628 DOI: 10.1097/md.0000000000032976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 01/24/2023] [Accepted: 01/25/2023] [Indexed: 02/25/2023] Open
Abstract
S100 family members (S100s) are small molecular EF hand calcium binding proteins and widely expressed in many tissues and organs. S100s are shown to be biomarkers of disease progression and prognosis in various types of cancers. Nevertheless, the expression patterns, function, and prognostic values of S100s and its association with tumor-infiltrating immune cells in pancreatic adenocarcinoma (PAAD) patients have not been systematically clarified. We explored the expression and roles of the entire 20 S100s in PAAD patients by using the following public databases: Oncomine, gene expression profiling interactive analysis, cBioPortal, Metascape, search tool for recurring instances of neighboring genes, Tumor IMmune Estimation Resource, and GeneMANIA. The S100A2/A3/A4/A6/A8/A9/A10/A11/A13/A14/A16/B/P mRNA expressions were significantly upregulated in PAAD patients. The mRNA expression of S100A3/A4/A5/A6/A10/A11/A14/A16/Z were significantly negatively related with the tumor stage in PAAD patients. We found that the S100A2/A3/A5/A10/A11/A14/A16 were significantly correlated with poor overall survival, whereas the increased levels of S100A1/B/G/Z were strongly associated with good overall survival. We found significant correlations among S100s and tumor-infiltrating immune cells. Cox proportional risk models revealed that B cells, Dendritic cells and S100A1/A5/A6/A8/A9/A13/A14 were significantly related with outcomes in PAAD patients. These results suggest that S100A2/A3/A10/A11/A14/A16 may serve as new diagnostic and prognostic biomarkers for PAAD patients and provide new clues for immunotherapy in PAAD patients.
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Affiliation(s)
- Yajun Ren
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Bing Chen
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Meng Zhang
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Key Clinical Laboratory of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Feng Xu
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Wang Y, Li N, Zhao J, Dai C. MiR-193a-5p serves as an inhibitor in ovarian cancer cells through RAB11A. Reprod Toxicol 2022; 110:105-112. [DOI: 10.1016/j.reprotox.2022.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 04/02/2022] [Accepted: 04/07/2022] [Indexed: 11/30/2022]
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A Novel Immune-Related Prognostic Signature Predicting Survival in Patients with Pancreatic Adenocarcinoma. JOURNAL OF ONCOLOGY 2022; 2022:8909631. [PMID: 35342420 PMCID: PMC8956421 DOI: 10.1155/2022/8909631] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 11/03/2021] [Accepted: 02/16/2022] [Indexed: 12/13/2022]
Abstract
Pancreatic adenocarcinoma (PAAD) carries the lowest survival rate of all major organ cancers, which is of dismal prognosis and high mortality rate. Thus, the present study attempted to identify a few novel prognostic biomarkers and establish an immune-related prognostic signature which could predict the prognosis of PAAD. Four prognostic immune-related genes (IRGs) including S100A6, S100A10, S100A16, and SDC1 were screened by differentially expressed gene (DEG) identification and weighted gene coexpression network analysis (WGCNA). Subsequent analysis proved the high expression of these IRGs in PAAD tissues, suggested by TCGA-PAAD data, merged microarray-acquired dataset (MMD), GEPIA, and Oncomine webtool. By using MMD and TCGA-PAAD data, S100A6 (MMD: AUC = 0.897; TCGA: AUC = 0.843), S100A10 (MMD: AUC = 0.880; TCGA: AUC = 0.780), S100A16 (MMD: AUC = 0.878; TCGA: AUC = 0.838), and SDC1 (MMD: AUC = 0.885; TCGA: AUC = 0.812) exhibited excellent diagnostic efficiency for PAAD. By conducting connectivity map (CMap) analysis, we concluded that three molecule drugs (sulpiride, famotidine, and nalidixic acid) might have worked in the treatment of PAAD. Then, an immune-related prognostic index was constructed, which was validated as an independent prognostic factor for PAAD patients (P=0.004). We further constructed a nomogram by using this immune-related signature and age, the prognostic value of which was validated by using concordance index (C-index = 0.780) and area under curve (AUC = 0.909). Moreover, the immune-related prognostic signature was associated with response to anti-PD-1/L1 immunotherapy. To sum up, four IRGs were screened out and verified to be novel immune-related prognostic biomarkers in PAAD. Besides, sulpiride, famotidine, and nalidixic acid might be potential choices in the treatment of PAAD. An immune-related signature was established to show great potential for prognosis prediction for PAAD, independently, which might guide more effective immunotherapy strategies. A nomogram is further established by using this immune-related prognostic index, which might contribute to more effective prognosis prediction in PAAD patients.
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6
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Li X, Qiu N, Li Q. Prognostic Values and Clinical Significance of S100 Family Member's Individualized mRNA Expression in Pancreatic Adenocarcinoma. Front Genet 2021; 12:758725. [PMID: 34804125 PMCID: PMC8595214 DOI: 10.3389/fgene.2021.758725] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 10/14/2021] [Indexed: 12/27/2022] Open
Abstract
Objective: Pancreatic adenocarcinoma (PAAD) is a common malignant tumor worldwide. S100 family (S100s) is wildly involved in regulating the occurrence, development, invasion, metastasis, apoptosis, and drug resistance of many malignant tumors. However, the expression pattern, prognostic value, and oncological role of individual S100s members in PAAD need to be elucidated. Methods: The transcriptional expression levels of S100s were analyzed through the Oncomine and GEPIA, respectively. The protein levels of S100s members in PAAD were studied by Human Protein Atlas. The correlation between S100 mRNA expression and overall survival and tumor stage in PAAD patients was studied by GEPIA. The transcriptional expression correlation and gene mutation rate of S100s members in PAAD patients were explored by cBioPortal. The co-expression networks of S100s are identified using STRING and Gene MANIA to predict their potential functions. The correlation of S100s expression and tumor-infiltrating immune cells was tested by TIMER. Pathway activity and drug target analyzed by GSCALite. Results: 13 S100s members were upregulated in PAAD tissues. 15 S100s members were associated with TP53 mutation. Expression levels of S100A3/A5/A6/A10/A11/A14/A16/B/P/Z were significantly correlated with the pathological stage. Prognosis analysis demonstrated that PAAD patients with low mRNA levels of S100A1/B/Z or high levels of S100A2/A3/A5/A10/A11/A14/A16 had a poor prognosis. Immuno-infiltration analysis showed that the mRNA levels of S100A10/A11/A14/A16 were correlated with the infiltration degree of macrophages in PAAD. Drug sensitivity analysis showed that PAAD expressing high levels of S100A2/A6/A10/A11/A13/A14/A16 maybe resistant to small molecule drugs. Conclusion: This study identifies the clinical significance and biological functions of the S100s in PAAD, which may provide novel insights for the selection of prognostic biomarkers.
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Affiliation(s)
- Xiaomin Li
- Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Ning Qiu
- Key Laboratory of Ocean and Marginal Sea Geology, Guangdong Southern Marine Science & Engineering Laboratory (Guangzhou), South China Sea Institute of Oceanology, Innovation Academy of South China Sea Ecology and Environmental Engineering, Chinese Academy of Sciences, Guangzhou, China
| | - Qijuan Li
- Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
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7
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Wu Y, Zhou Q, Guo F, Chen M, Tao X, Dong D. S100 Proteins in Pancreatic Cancer: Current Knowledge and Future Perspectives. Front Oncol 2021; 11:711180. [PMID: 34527585 PMCID: PMC8435722 DOI: 10.3389/fonc.2021.711180] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 08/12/2021] [Indexed: 12/25/2022] Open
Abstract
Pancreatic cancer (PC) is a highly malignant tumor occurring in the digestive system. Currently, there is a lack of specific and effective interventions for PC; thus, further exploration regarding the pathogenesis of this malignancy is warranted. The S100 protein family, a collection of calcium-binding proteins expressed only in vertebrates, comprises 25 members with high sequence and structural similarity. Dysregulated expression of S100 proteins is a biomarker of cancer progression and prognosis. Functionally, these proteins are associated with the regulation of multiple cellular processes, including proliferation, apoptosis, growth, differentiation, enzyme activation, migration/invasion, Ca2+ homeostasis, and energy metabolism. This review highlights the significance of the S100 family in the diagnosis and prognosis of PC and its vital functions in tumor cell metastasis, invasion and proliferation. A further understanding of S100 proteins will provide potential therapeutic targets for preventing or treating PC.
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Affiliation(s)
- Yu Wu
- Department of Clinical Pharmacy, First Affiliated Hospital of Dalian Medical University, Dalian, China.,College of Pharmacy, Dalian Medical University, Dalian, China
| | - Qi Zhou
- Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Fangyue Guo
- Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Mingming Chen
- Department of Clinical Pharmacy, First Affiliated Hospital of Dalian Medical University, Dalian, China.,College of Pharmacy, Dalian Medical University, Dalian, China
| | - Xufeng Tao
- School of Chemical Engineering, Dalian University of Technology, Dalian, China
| | - Deshi Dong
- Department of Clinical Pharmacy, First Affiliated Hospital of Dalian Medical University, Dalian, China
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Wang T, Han S, Du G. S100A6 represses Calu-6 lung cancer cells growth via inhibiting cell proliferation, migration, invasion and enhancing apoptosis. Cell Biochem Funct 2021; 39:771-779. [PMID: 34008212 PMCID: PMC8453982 DOI: 10.1002/cbf.3639] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 04/17/2021] [Accepted: 04/19/2021] [Indexed: 11/10/2022]
Abstract
S100 calcium binding protein A6 (S100A6) has been reported to involve in many kinds of cancers through regulating intracellular calcium homeostasis. Previous studies found that S100A6 increased in lung cancer patients' plasma and pleural effusion. This study focused on its function in Calu-6 lung cancer cells. S100A6 gene was transferred into Calu-6 lung cancer cell line by lentivirus vector, the empty vector transfected cells and the blank cells were set as control groups. MTT was evaluating cell proliferation. The transwell assay was reflecting cell migration and cell invasion. The flow cytometric analysis was detecting cell apoptosis and cell cycle of three groups (Calu-6, Calu-6/neo, Calu-6/S100A6). Nude mouse tumorigenicity was then applied to evaluate S100A6's effect on cellular tumorigenicity. Compared with control groups, Calu-6/S100A6 cells showed a weakening trend in the cell behaviours of proliferation, migration and invasiveness, while had an enhancement of cell apoptosis, with all P < .05. The cell cycle of Calu-6/S100A6 cells had a reduction of S phase and an increase of G1 phase (P < .05). In animal study, after 5 weeks of cell injection, the tumour bulk of Calu-6/S100A6 group was smaller than controls, with P < .05. Our results demonstrate S100A6 inhibits the growth of Calu-6 lung cancer cells, as well as impairs Calu-6's ability in tumorigenesis. At cellular level, S100A6 is supposed to act as a tumour suppressor gene in lung cancer.
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Affiliation(s)
- Ting Wang
- Department of Respiratory Medicine, Xi'an People's Hospital (Xi'an No.4 Hospital), Xi'an, China
| | - Suoli Han
- Department of Oncology, Zibo Mining Coal Hospital, Zibo, China
| | - Ge Du
- Department of Rehabilitation Center for Elderly, Beijing Rehabilitation Hospital Affiliated to Capital Medical University, Beijing, China
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Development of a prognostic model based on an immunogenomic landscape analysis of medulloblastoma. Biosci Rep 2021; 41:227393. [PMID: 33345275 PMCID: PMC7791544 DOI: 10.1042/bsr20202907] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 12/02/2020] [Accepted: 12/16/2020] [Indexed: 11/17/2022] Open
Abstract
Medulloblastoma (MB) is one of the most common central nervous system tumors in children. At present, the vital role of immune abnormalities has been proved in tumorigenesis and progression. However, the immune mechanism in MB is still poorly understood. In the present study, 51 differentially expressed immune-related genes (DE-IRGs) and 226 survival associated immune-related genes (Sur-IRGs) were screened by an integrated analysis of multi-array. Moreover, the potential pathways were enriched by functional analysis, such as ‘cytokine–cytokine receptor interaction’, ‘Ras signaling pathway’, ‘PI3K-Akt signaling pathway’ and ‘pathways in cancer’. Furthermore, 10 core IRGs were identified from DE-IRGs and Sur-IRGs. And the potential regulatory mechanisms of core IRGs were also explored. Additionally, a new prognostic model, including 7 genes (HDGF, CSK, PNOC, S100A13, RORB, FPR1, and ICAM2) based on IRGs, was established by multivariable COX analysis. In summary, our study revealed the underlying immune mechanism of MB. Moreover, we developed a prognostic model associated with clinical characteristics and could reflect the infiltration of immune cells.
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An Integrated Bioinformatic Analysis of the S100 Gene Family for the Prognosis of Colorectal Cancer. BIOMED RESEARCH INTERNATIONAL 2020; 2020:4746929. [PMID: 33294444 PMCID: PMC7718059 DOI: 10.1155/2020/4746929] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Accepted: 10/28/2020] [Indexed: 11/23/2022]
Abstract
Background S100 family genes exclusively encode at least 20 calcium-binding proteins, which possess a wide spectrum of intracellular and extracellular functions in vertebrates. Multiple lines of evidences suggest that dysregulated S100 proteins are associated with human malignancies including colorectal cancer (CRC). However, the diverse expression patterns and prognostic roles of distinct S100 genes in CRC have not been fully elucidated. Methods In the current study, we analyzed the mRNA expression levels of S100 family genes and proteins and their associations with the survival of CRC patients using the Oncomine analysis and GEPIA databases. Expressions and mutations of S100 family genes were analyzed using the cBioPortal, and protein-protein interaction (PPI) networks of S100 proteins and their mutation-related coexpressed genes were analyzed using STRING and Cytoscape. Results We observed that the mRNA expression levels of S100A2, S100A3, S100A9, S100A11, and S100P were higher and the level of S100B was lower in CRC tissues than those in normal colon mucosa. A high S100A10 levels was associated with advanced-stage CRC. Results from GEPIA database showed that highly expressed S100A1 was correlated with worse overall survival (OS) and disease-free survival (DFS) and that overexpressions of S100A2 and S100A11 were associated with poor DFS of CRC, indicating that S100A1, S100A2, and S100A11 are potential prognostic markers. Unexpectedly, most of S100 family genes showed no significant prognostic values in CRC. Conclusions Our findings, though still need to be ascertained, offer novel insights into the prognostic implications of the S100 family in CRC and will inspire more clinical trials to explore potential S100-targeted inhibitors for the treatment of CRC.
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Xu HY, Song HM, Zhou Q. Comprehensive analysis of the expression and prognosis for S100 in human ovarian cancer: A STROBE study. Medicine (Baltimore) 2020; 99:e22777. [PMID: 33217795 PMCID: PMC7676574 DOI: 10.1097/md.0000000000022777] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
S100 family members are frequently deregulated in human malignancies, including ovarian cancer. However, the prognostic roles of each individual S100 family member in ovarian cancer (OC) patients remain elusive. In the present study, we assessed the prognostic roles and molecular function of 20 individual members of the S100 family in OC patients using GEPIA, Kaplan-Meier plotter, SurvExpress, GeneMANIA and Funrich database. Our results indicated that the mRNA expression levels of S100A1, S100A2, S100A4, S100A5, S100A11, S100A14, and S100A16 were significantly upregulated in patients with OC, and high mRNA expression of S100A1, S100A3, S100A5, S100A6, and S100A13 were significantly correlated with better overall survival, while increased S100A2, S100A7A, S100A10, and S100A11 mRNA expressions were associated with worse prognosis in OC patients. In stratified analysis, the trends of high expression of individual S100 members were nearly the same in different pathological grade, clinical stage, TP53 mutation status, and treatment. More importantly, S100 family signatures may be useful potential prognostic markers for OC. These findings suggest that S100 family plays a vital role in prognostic value and could potentially be an S100-targeted inhibitors for OC patients.
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Affiliation(s)
- Hong-Yu Xu
- Department of Gynecology and Obstetrics, the Second People's Hospital of Yichang, China Three Gorges University
| | - Hua-Mei Song
- Department of Gynecology and Obstetrics, the People's Hospital of China Three Gorges University/the First People's Hospital of Yichang, Yichang, Hubei, China
| | - Quan Zhou
- Department of Gynecology and Obstetrics, the People's Hospital of China Three Gorges University/the First People's Hospital of Yichang, Yichang, Hubei, China
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12
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Allgöwer C, Kretz AL, von Karstedt S, Wittau M, Henne-Bruns D, Lemke J. Friend or Foe: S100 Proteins in Cancer. Cancers (Basel) 2020; 12:cancers12082037. [PMID: 32722137 PMCID: PMC7465620 DOI: 10.3390/cancers12082037] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 07/21/2020] [Accepted: 07/23/2020] [Indexed: 12/24/2022] Open
Abstract
S100 proteins are widely expressed small molecular EF-hand calcium-binding proteins of vertebrates, which are involved in numerous cellular processes, such as Ca2+ homeostasis, proliferation, apoptosis, differentiation, and inflammation. Although the complex network of S100 signalling is by far not fully deciphered, several S100 family members could be linked to a variety of diseases, such as inflammatory disorders, neurological diseases, and also cancer. The research of the past decades revealed that S100 proteins play a crucial role in the development and progression of many cancer types, such as breast cancer, lung cancer, and melanoma. Hence, S100 family members have also been shown to be promising diagnostic markers and possible novel targets for therapy. However, the current knowledge of S100 proteins is limited and more attention to this unique group of proteins is needed. Therefore, this review article summarises S100 proteins and their relation in different cancer types, while also providing an overview of novel therapeutic strategies for targeting S100 proteins for cancer treatment.
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Affiliation(s)
- Chantal Allgöwer
- Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (C.A.); (A.-L.K.); (M.W.); (D.H.-B.)
| | - Anna-Laura Kretz
- Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (C.A.); (A.-L.K.); (M.W.); (D.H.-B.)
| | - Silvia von Karstedt
- Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University Hospital Cologne, Weyertal 115b, 50931 Cologne, Germany;
- CECAD Cluster of Excellence, University of Cologne, Joseph-Stelzmann-Straße 26, 50931 Cologne, Germany
- Center of Molecular Medicine Cologne, Medical Faculty, University Hospital of Cologne, Weyertal 115b, 50931 Cologne, Germany
| | - Mathias Wittau
- Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (C.A.); (A.-L.K.); (M.W.); (D.H.-B.)
| | - Doris Henne-Bruns
- Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (C.A.); (A.-L.K.); (M.W.); (D.H.-B.)
| | - Johannes Lemke
- Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (C.A.); (A.-L.K.); (M.W.); (D.H.-B.)
- Correspondence: ; Tel.: +49-731-500-53691
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Wu JL, Zhao J, Zhang HB, Zuo WW, Li Y, Kang S. Genetic variants and expression of the TIM-3 gene are associated with clinical prognosis in patients with epithelial ovarian cancer. Gynecol Oncol 2020; 159:270-276. [PMID: 32694063 DOI: 10.1016/j.ygyno.2020.07.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 07/06/2020] [Indexed: 01/17/2023]
Abstract
OBJECTIVE Polymorphisms of T cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) were reported to be associated with cancer risk and patients' survival. This study aims to investigate the correlation of TIM-3 polymorphisms with susceptibility to epithelial ovarian cancer (EOC) and patients' outcomes. METHODS A total of 700 EOC patients and 710 healthy controls from North China were included. The polymorphisms (rs10053538, rs10515746 and rs1036199) were genotyped using the polymerase chain reaction/ligase detection reaction (PCR-LDR) method. Survival data were available for 339 patients after cytoreductive surgery. The expression level of TIM-3 was detected by real-time quantitative PCR (RT-qPCR). The prognostic value of TIM3 in EOC patients was assessed using the Kaplan-Meier plotter database. RESULTS The results showed that none of the TIM3 polymorphisms were associated with the risk of developing EOC. Patients with the rs10053538 CA + AA genotype had worse PFS and OS than those with the CC genotype (HR = 1.49, 95% CI = 1.05-2.09, P = 0.024 and HR = 1.57, 95%CI = 1.09-2.26, P = 0.017, respectively). The RT-qPCR results showed that the expression levels of TIM-3 mRNA in EOC tissues with the rs10053538CA + AA genotypes were significantly higher than those with the CC genotype (P = 0.006). Analysis using the Kaplan-Meier plotter database showed that high expression of TIM-3 mRNA was significantly associated with shorter PFS and OS in EOC patients (HR = 1.57, 95%CI = 1.29-1.91, P < 0.001 and HR = 1.31, 95% CI = 1.06-1.63, P = 0.013, respectively). CONCLUSIONS TIM-3 polymorphisms were not associated with risk of developing EOC. Both rs10053538 and the expression level of TIM-3 mRNA may be associated with its clinical outcome in EOC patients.
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Affiliation(s)
- Jian-Lei Wu
- Department of Obstetrics and Gynaecology, Hebei Medical University, Fourth Hospital, Shijiazhuang, China
| | - Jian Zhao
- Department of Obstetrics and Gynaecology, First Hospital of Shijiazhuang, Shijiazhuang, China
| | - Hai-Bo Zhang
- Department of Obstetrics and Gynaecology, Hebei Medical University, Fourth Hospital, Shijiazhuang, China
| | - Wei-Wei Zuo
- Department of Obstetrics and Gynaecology, Hebei Medical University, Fourth Hospital, Shijiazhuang, China
| | - Yan Li
- Department of Molecular Biology, Hebei Medical University, Fourth Hospital, Shijiazhuang, China.
| | - Shan Kang
- Department of Obstetrics and Gynaecology, Hebei Medical University, Fourth Hospital, Shijiazhuang, China.
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