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Borea R, Reduzzi C. The growing field of liquid biopsy and its Snowball effect on reshaping cancer management. THE JOURNAL OF LIQUID BIOPSY 2025; 8:100293. [PMID: 40255897 PMCID: PMC12008596 DOI: 10.1016/j.jlb.2025.100293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Revised: 03/24/2025] [Accepted: 03/24/2025] [Indexed: 04/22/2025]
Abstract
Liquid biopsy (LB) has emerged as a transformative tool in oncology, providing a minimally invasive approach for tumor detection, molecular characterization, and real-time treatment monitoring. By analyzing circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), extracellular vesicles (EVs), and microRNA (miRNA), LB enables comprehensive tumor profiling without the need for traditional tissue biopsies. Over the past decade, research in this field has expanded exponentially, leading to the integration of LB into clinical practice for specific cancer types, including lung and breast cancer. In 2024, the Journal of Liquid Biopsy (JLB) published innovative studies exploring the latest advancements in LB technologies, biomarkers, and their applications for cancer detection, minimal residual disease (MRD) monitoring, and therapy response assessment. This review synthesizes recent findings on the role of LB in cancer treatment and monitoring across different biomarkers, with a particular focus on newly published studies and their context within translational research. Additionally, it highlights emerging techniques such as fragmentomics, artificial intelligence, and multiomics, paving the way for more precise, personalized treatment decisions. Despite these advancements, challenges remain in standardizing methodologies, optimizing clinical validation, and integrating LB into routine oncological workflows. This mini-review highlights the evolving landscape of LB research and its potential to revolutionize cancer diagnosis, treatment monitoring, and therapeutic decision-making, ushering in a new era of precision oncology.
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Affiliation(s)
- Roberto Borea
- Department of Public Health, University Federico II of Naples, Naples, Italy
- Department of Internal Medicine and Medical Sciences (DiMI), School of Medicine, University of Genova, Genova, Italy
| | - Carolina Reduzzi
- Department of Medicine, Weill Cornell Medicine, Englander Institute for Precision Medicine, New York Presbyterian Hospital, New York, NY, 10021, USA
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2
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Holbrook KL, Lee WY. Volatile Organic Metabolites as Potential Biomarkers for Genitourinary Cancers: Review of the Applications and Detection Methods. Metabolites 2025; 15:37. [PMID: 39852380 PMCID: PMC11767221 DOI: 10.3390/metabo15010037] [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: 12/04/2024] [Revised: 01/07/2025] [Accepted: 01/08/2025] [Indexed: 01/26/2025] Open
Abstract
Cancer is one of the leading causes of death globally, and is ranked second in the United States. Early detection is crucial for more effective treatment and a higher chance of survival rates, reducing burdens on individuals and societies. Genitourinary cancers, in particular, face significant challenges in early detection. Finding new and cost-effective diagnostic methods is of clinical need. Metabolomic-based approaches, notably volatile organic compound (VOC) analysis, have shown promise in detecting cancer. VOCs are small organic metabolites involved in biological processes and disease development. They can be detected in urine, breath, and blood samples, making them potential candidates for sensitive and non-invasive alternatives for early cancer detection. However, developing robust VOC detection methods remains a hurdle. This review outlines the current landscape of major genitourinary cancers (kidney, prostate, bladder, and testicular), including epidemiology, risk factors, and current diagnostic tools. Furthermore, it explores the applications of using VOCs as cancer biomarkers, various analytical techniques, and comparisons of extraction and detection methods across different biospecimens. The potential use of VOCs in detection, monitoring disease progression, and treatment responses in the field of genitourinary oncology is examined.
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Affiliation(s)
| | - Wen-Yee Lee
- Department of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, TX 79968, USA;
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3
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Wang Z, Xie C, Chen X. Diagnostic and therapeutic role of non-coding RNAs regulating programmed cell death in melanoma. Front Oncol 2024; 14:1476684. [PMID: 39777348 PMCID: PMC11703721 DOI: 10.3389/fonc.2024.1476684] [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: 08/06/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
lncRNAs (long non-coding RNAs) are heterogeneous RNA molecules that modulate various cellular processes, such as proliferation, differentiation, migration, invasion, and apoptosis, via different mechanisms. An increasing amount of research indicates that abnormal expression of lncRNA influences the development of drug resistance as well as the genesis and advancement of cancer, including melanoma. Furthermore, they are attractive biomarkers for non-invasive cancer diagnostics due to their strongly modulated expression and improved tissue and disease specificity. This review offers a succinct overview of the present understanding concerning the potential diagnostic biomarker potential of lncRNAs in melanoma. Cell death occurs frequently during growth and throughout life and is an active, organized, and genetically determined process. It is essential for the regulation of homeostasis. Controlled cell death and non-programmed cell death are both forms of cell death. The most prevalent forms of regulatory cell death are pyroptosis, ferroptosis, autophagy, necroptosis, necrosis, and apoptosis. Ferroptosis, pyroptosis, and autophagy are less common forms of cell death compared to necrosis, apoptosis, and necroptosis. ncRNAs are regulatory RNA molecules that are not involved in encoding proteins. They primarily consist of circular RNAs (circ RNAs), lncRNAs, and microRNAs (miRNAs). Moreover, non-coding RNAs have the ability to modulate tumor cell autophagy, pyroptosis, and ferroptosis at the transcriptional or post-transcriptional stage, as well as function as oncogenes and tumor suppressor genes, which can have considerable effects on the incidence and growth of tumors. This review concentrated on the recent advancements in the research of the diagnostic and therapeutic functions of ncRNAs in the regulation of programmed cell death in melanoma.
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Affiliation(s)
- Zixu Wang
- Office for Doctoral Studies, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Cong Xie
- Office for Doctoral Studies, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Xiao Chen
- Office for Postgraduate Student Studies, Kunming Medical University, Kunming, China
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Pilotto Heming C, Aran V. The potential of circulating cell-free RNA in CNS tumor diagnosis and monitoring: A liquid biopsy approach. Crit Rev Oncol Hematol 2024; 204:104504. [PMID: 39251048 DOI: 10.1016/j.critrevonc.2024.104504] [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: 06/21/2024] [Revised: 08/20/2024] [Accepted: 09/04/2024] [Indexed: 09/11/2024] Open
Abstract
Early detection of malignancies, through regular cancer screening, has already proven to have potential to increase survival rates. Yet current screening methods rely on invasive, expensive tissue sampling that has hampered widespread use. Liquid biopsy is noninvasive and represents a potential approach to precision oncology, based on molecular profiling of body fluids. Among these, circulating cell-free RNA (cfRNA) has gained attention due to its diverse composition and potential as a sensitive biomarker. This review provides an overview of the processes of cfRNA delivery into the bloodstream and the role of cfRNA detection in the diagnosis of central nervous system (CNS) tumors. Different types of cfRNAs such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been recognized as potential biomarkers in CNS tumors. These molecules exhibit differential expression patterns in the plasma, cerebrospinalfluid (CSF) and urine of patients with CNS tumors, providing information for diagnosing the disease, predicting outcomes, and assessing treatment effectiveness. Few clinical trials are currently exploring the use of liquid biopsy for detecting and monitoring CNS tumors. Despite obstacles like sample standardization and data analysis, cfRNA shows promise as a tool in the diagnosis and management of CNS tumors, offering opportunities for early detection, personalized therapy, and improved patient outcomes.
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Affiliation(s)
- Carlos Pilotto Heming
- Programa de Pós-Graduação em Anatomia Patológica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro (UFRJ), Av. Rodolpho Paulo Rocco 225, Rio de Janeiro 21941-905, Brazil; Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Rua do Rezende 156, Rio de Janeiro 20231-092, Brazil
| | - Veronica Aran
- Programa de Pós-Graduação em Anatomia Patológica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro (UFRJ), Av. Rodolpho Paulo Rocco 225, Rio de Janeiro 21941-905, Brazil; Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Rua do Rezende 156, Rio de Janeiro 20231-092, Brazil.
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5
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Hu B, Zhang Y, Jiang B, Li A. Prognostic value of circulating long non-coding RNAs in colorectal cancer patients: a meta-analysis. Expert Rev Anticancer Ther 2024; 24:1249-1259. [PMID: 37934874 DOI: 10.1080/14737140.2023.2280643] [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: 11/01/2022] [Accepted: 10/27/2023] [Indexed: 11/09/2023]
Abstract
OBJECTIVES This meta-analysis aimed to evaluate the prognostic significance of circulating long non-coding RNAs (lncRNAs) in colorectal cancer (CRC). METHODS A comprehensive literature search was conducted in databases (Embase, Web of Science, PubMed, and Cochrane Library) up to July 2022. The quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Statistical analysis was performed with Review Manager 5.4 and Stata 17.0. Publication bias was assessed using Begg's test, and sensitivity analysis was conducted to validate the meta-analysis results. RESULTS Ten articles, comprising 1,473 CRC patients and 18 different circulating lncRNAs, were included. Thirteen circulating lncRNAs were found to be up-regulated in CRC patients, while five were down-regulated. High expression of circulating lncRNAs up-regulated in CRC patients was associated with shorter CRC OS (HR = 2.91, 95% CI: 1.17, 7.22; P = 0.02, I2 = 86%). Conversely, high expression of circulating lncRNAs down-regulated in CRC patients was linked to longer CRC OS (HR = 0.16, 95% CI: 0.07, 0.40; P < 0.0001, I2 = 0%) and improved DFS (HR = 0.52, 95% CI: 0.37, 0.74; P = 0.0002, I2 = 0%). Additionally, circulating lncRNA levels correlated with TNM staging, tumor location, and lymph node metastasis. CONCLUSION Circulating lncRNAs show promise as prognostic markers for CRC patients, but further studies are warranted to validate these findings.
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Affiliation(s)
- Bin Hu
- Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
| | - Yanfei Zhang
- Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
| | - Bingjing Jiang
- Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
| | - Angcheng Li
- Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
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Albitar M, Charifa A, Agersborg S, Pecora A, Ip A, Goy A. Expanding the clinical utility of liquid biopsy by using liquid transcriptome and artificial intelligence. THE JOURNAL OF LIQUID BIOPSY 2024; 6:100270. [PMID: 40027317 PMCID: PMC11863701 DOI: 10.1016/j.jlb.2024.100270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 10/14/2024] [Accepted: 10/14/2024] [Indexed: 03/05/2025]
Abstract
Most of the current utilization of liquid biopsy (LBx) is based on analyzing cell-free DNA(cfDNA). There is limited data on using cell-free RNA (cfRNA) levels (liquid transcriptome) in LBx. The major hurdles for using liquid transcriptome is its low level in circulation and the dilutional effects of various tissues that may pour their RNA into circulation. We explored the potential of using artificial intelligence (AI) to normalize the cancer-specific cfRNA and to enable liquid transcriptome to predict diagnosis. cfRNA transcriptomic data from 1009 peripheral blood samples was generated by hybrid capture next generation sequencing (NGS). Using two-thirds of samples for training and one third for testing, we demonstrate that AI is able to distinguish between normal control (N = 368) and patients with solid tumors (N = 404) with AUC = 0.820 (95 % CI: 0.760-0.879), patients with myeloid neoplasms (N = 99) with AUC = 0.858 (95 % CI: 0.793-0.924) and patients with lymphoid neoplasms (N = 128) with AUC = 0.788 (95 % CI: 0.687-0.888). Specific diagnosis was also possible when patients with lung, breast, colorectal, and myelodysplastic subgroups were tested. This data suggests that liquid transcriptomics when used with AI has the potential of transforming "liquid biopsy" to "true" biopsy, replacing the need for tissue biopsy.
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Affiliation(s)
| | | | | | | | - Andrew Ip
- John Theurer Cancer Center, Hackensack, NJ, USA
| | - Andre Goy
- John Theurer Cancer Center, Hackensack, NJ, USA
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Shen M, Chen M, Chen Y, Yu Y. Mitophagy related diagnostic biomarkers for coronary in-stent restenosis identified using machine learning and bioinformatics. Sci Rep 2024; 14:24137. [PMID: 39406802 PMCID: PMC11480419 DOI: 10.1038/s41598-024-74862-y] [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: 08/04/2024] [Accepted: 09/30/2024] [Indexed: 10/19/2024] Open
Abstract
Percutaneous coronary intervention (PCI) combined with stent implantation is currently one of the most effective treatments for coronary artery disease (CAD). However, in-stent restenosis (ISR) significantly compromises its long-term efficacy. Mitophagy plays a crucial role in vascular homeostasis, yet its role in ISR remains unclear. This study aims to identify mitophagy-related biomarkers for ISR and explore their underlying molecular mechanisms. Through differential gene expression analysis between ISR and Control samples in the combined dataset, 169 differentially expressed genes (DEGs) were identified. Twenty-three differentially expressed mitophagy-related genes (DEMRGs) were identified by intersecting with mitophagy-related genes (MRGs) from the GeneCards, and functional enrichment analysis indicated their significant involvement in mitophagy-related biological processes. Using Weighted Gene Co-expression Network Analysis (WGCNA) and three machine learning algorithms (Logistic-LASSO, RF, and SVM-RFE), LRRK2, and ANKRD13A were identified as mitophagy-related biomarkers for ISR. The nomogram based on these two genes also exhibited promising diagnostic performance for ISR. Gene Set Enrichment Analysis (GSEA) as well as immune infiltration analyses showed that these two genes were closely associated with immune and inflammatory responses in ISR. Furthermore, potential small molecule compounds with therapeutic implications for ISR were predicted using the connectivity Map (cMAP) database. This study systematically investigated mitophagy-related biomarkers for ISR and their potential biological functions, providing new insights into early diagnosis and precision treatment strategies for ISR.
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Affiliation(s)
- Ming Shen
- Department of Cardiology, the 926th Hospital of the Joint Logistic Support Force of PLA, Affiliated Hospital of Kunming University of Science and Technology, Kaiyuan, 661600, Yunnan, China.
- Department of Cardiology, the 920th Hospital of the Joint Logistic Support Force of PLA, Kunming, 650032, Yunnan, China.
| | - Meixian Chen
- Department of Cardiology, Fuzong Clinical Medical College of Fujian Medical University (900th Hospital of the Joint Logistic Support Force of PLA), Fuzhou, 350025, Fujian, China
| | - Yu Chen
- Department of Cardiology, the 920th Hospital of the Joint Logistic Support Force of PLA, Kunming, 650032, Yunnan, China
| | - Yunhua Yu
- Department of Geriatric, Fuzong Clinical Medical College of Fujian Medical University (900th Hospital of the Joint Logistic Support Force of PLA), Fuzhou, 350025, Fujian, China.
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8
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Lin Y, Zhao W, Pu R, Lv Z, Xie H, Li Y, Zhang Z. Long non‑coding RNAs as diagnostic and prognostic biomarkers for colorectal cancer (Review). Oncol Lett 2024; 28:486. [PMID: 39185489 PMCID: PMC11342420 DOI: 10.3892/ol.2024.14619] [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: 05/11/2024] [Accepted: 07/29/2024] [Indexed: 08/27/2024] Open
Abstract
Colorectal cancer (CRC) ranks as the 3rd most common cancer globally and is the 2nd leading cause of cancer-related death. Owing to the lack of specific early symptoms and the limitations of existing early diagnostic methods, most patients with CRC are diagnosed at advanced stages. To overcome these challenges, researchers have increasingly focused on molecular biomarkers, with particular interest in long non-coding RNAs (lncRNAs). These non-protein-coding RNAs, which exceed 200 nucleotides in length, play critical roles in the development and progression of CRC. The stability and detectability of lncRNAs in the circulatory system make them promising candidate biomarkers. The analysis of circulating lncRNAs in peripheral blood represents a potential option for minimally invasive diagnostic tests based on liquid biopsy samples. The present review aimed to evaluate the efficacy of lncRNAs with altered expression levels in peripheral blood as diagnostic markers for CRC. Additionally, the clinical significance of lncRNAs as prognostic markers for this disease were summarized.
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Affiliation(s)
- Yuning Lin
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian 361009, P.R. China
| | - Wenzhen Zhao
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian 361009, P.R. China
| | - Ruonan Pu
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian 361009, P.R. China
| | - Zhenyi Lv
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian 361009, P.R. China
| | - Hongyan Xie
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian 361009, P.R. China
| | - Ying Li
- Department of Ultrasonography, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Zhongying Zhang
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian 361009, P.R. China
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Decruyenaere P, Daneels W, Morlion A, Verniers K, Anckaert J, Tavernier J, Offner F, Vandesompele J. Characterizing the Cell-Free Transcriptome in a Humanized Diffuse Large B-Cell Lymphoma Patient-Derived Tumor Xenograft Model for RNA-Based Liquid Biopsy in a Preclinical Setting. Int J Mol Sci 2024; 25:9982. [PMID: 39337470 PMCID: PMC11432451 DOI: 10.3390/ijms25189982] [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: 08/20/2024] [Revised: 09/04/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
The potential of RNA-based liquid biopsy is increasingly being recognized in diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma. This study explores the cell-free transcriptome in a humanized DLBCL patient-derived tumor xenograft (PDTX) model. Blood plasma samples (n = 171) derived from a DLBCL PDTX model, including 27 humanized (HIS) PDTX, 8 HIS non-PDTX, and 21 non-HIS PDTX non-obese diabetic (NOD)-scid IL2Rgnull (NSG) mice were collected during humanization, xenografting, treatment, and sacrifice. The mice were treated with either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), CD20-targeted human IFNα2-based AcTaferon combined with CHOP (huCD20-Fc-AFN-CHOP), or phosphate-buffered saline (PBS). RNA was extracted using the miRNeasy serum/plasma kit and sequenced on the NovaSeq 6000 platform. RNA sequencing data of the formalin-fixed paraffin-embedded (FFPE) tissue and blood plasma samples of the original patient were included. Flow cytometry was performed on immune cells isolated from whole blood, spleen, and bone marrow. Bulk deconvolution was performed using the Tabula Sapiens v1 basis matrix. Both R-CHOP and huCD20-Fc-AFN-CHOP were able to control tumor growth in most mice. Xenograft tumor volume was strongly associated with circulating tumor RNA (ctRNA) concentration (p < 0.001, R = 0.89), as well as with the number of detected human genes (p < 0.001, R = 0.79). Abundance analysis identified tumor-specific biomarkers that were dynamically tracked during tumor growth or treatment. An 8-gene signature demonstrated high accuracy for assessing therapy response (AUC 0.92). The tumoral gene detectability in the ctRNA of the PDTX-derived plasma was associated with RNA abundance levels in the patient's tumor tissue and blood plasma (p < 0.001), confirming that tumoral gene abundance contributes to the cell-free RNA (cfRNA) profile. Decomposing the transcriptome, however, revealed high inter- and intra-mouse variability, which was lower in the HIS PDTX mice, indicating an impact of human engraftment on the stability and profile of cfRNA. Immunochemotherapy resulted in B cell depletion, and tumor clearance was reflected by a decrease in the fraction of human CD45+ cells. Lastly, bulk deconvolution provided complementary biological insights into the composition of the tumor and circulating immune system. In conclusion, the blood plasma-derived transcriptome serves as a biomarker source in a preclinical PDTX model, enables the assessment of biological pathways, and enhances the understanding of cfRNA dynamics.
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Affiliation(s)
- Philippe Decruyenaere
- Department of Hematology, Ghent University Hospital, 9000 Ghent, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium
- Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium
| | - Willem Daneels
- Department of Hematology, Ghent University Hospital, 9000 Ghent, Belgium
- Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium
- VIB-UGent Center for Medical Biotechnology, 9052 Ghent, Belgium
| | - Annelien Morlion
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium
- Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium
| | - Kimberly Verniers
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium
- Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium
| | - Jasper Anckaert
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium
- Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium
| | - Jan Tavernier
- Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium
- VIB-UGent Center for Medical Biotechnology, 9052 Ghent, Belgium
- Orionis Biosciences B.V., 9052 Zwijnaarde, Belgium
| | - Fritz Offner
- Department of Hematology, Ghent University Hospital, 9000 Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium
| | - Jo Vandesompele
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium
- Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium
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10
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Song X, Li J, Zhu J, Kong YF, Zhou YH, Wang ZK, Zhang J. Predictors of early colorectal cancer metastasis to lymph nodes: providing rationale for therapy decisions. Front Oncol 2024; 14:1371599. [PMID: 39035744 PMCID: PMC11257837 DOI: 10.3389/fonc.2024.1371599] [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: 01/17/2024] [Accepted: 06/24/2024] [Indexed: 07/23/2024] Open
Abstract
With the improvement of national health awareness and the popularization of a series of screening methods, the number of patients with early colorectal cancer is gradually increasing, and accurate prediction of lymph node metastasis of T1 colorectal cancer is the key to determining the optimal therapeutic solutions. Whether patients with T1 colorectal cancer undergoing endoscopic resection require additional surgery and regional lymph node dissection is inconclusive in current guidelines. However, we can be sure that in early colorectal cancer without lymph node metastasis, endoscopic resection alone does not affect the prognosis, and it greatly improves the quality of life and reduces the incidence of surgical complications while preserving organ integrity. Therefore, it is vital to discriminate patients without lymph node metastasis in T1 colorectal cancer, and this requires accurate predictors. This paper briefly explains the significance and shortcomings of traditional pathological factors, then extends and states the new pathological factors, clinical test factors, molecular biomarkers, and the risk assessment models of lymph node metastasis based on artificial intelligence.
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Affiliation(s)
| | | | | | | | | | | | - Jin Zhang
- Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
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11
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Lin Y, Zhao W, Lv Z, Xie H, Li Y, Zhang Z. The functions and mechanisms of long non-coding RNA in colorectal cancer. Front Oncol 2024; 14:1419972. [PMID: 39026978 PMCID: PMC11254705 DOI: 10.3389/fonc.2024.1419972] [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: 04/19/2024] [Accepted: 06/18/2024] [Indexed: 07/20/2024] Open
Abstract
CRC poses a significant challenge in the global health domain, with a high number of deaths attributed to this disease annually. If CRC is detected only in its advanced stages, the difficulty of treatment increases significantly. Therefore, biomarkers for the early detection of CRC play a crucial role in improving patient outcomes and increasing survival rates. The development of a reliable biomarker for early detection of CRC is particularly important for timely diagnosis and treatment. However, current methods for CRC detection, such as endoscopic examination, blood, and stool tests, have certain limitations and often only detect cases in the late stages. To overcome these constraints, researchers have turned their attention to molecular biomarkers, which are considered a promising approach to improving CRC detection. Non-invasive methods using biomarkers such as mRNA, circulating cell-free DNA, microRNA, LncRNA, and proteins can provide more reliable diagnostic information. These biomarkers can be found in blood, tissue, stool, and volatile organic compounds. Identifying molecular biomarkers with high sensitivity and specificity for the early and safe, economic, and easily measurable detection of CRC remains a significant challenge for researchers.
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Affiliation(s)
- Yuning Lin
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, China
| | - Wenzhen Zhao
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, China
| | - Zhenyi Lv
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, China
| | - Hongyan Xie
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, China
| | - Ying Li
- Ultrasonography Department, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Zhongying Zhang
- Medical Laboratory, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, China
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12
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Katifelis H, Gazouli M. RNA biomarkers in cancer therapeutics: The promise of personalized oncology. Adv Clin Chem 2024; 123:179-219. [PMID: 39181622 DOI: 10.1016/bs.acc.2024.06.003] [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] [Indexed: 08/27/2024]
Abstract
Cancer therapy is a rapidly evolving and constantly expanding field. Current approaches include surgery, conventional chemotherapy and novel biologic agents as in immunotherapy, that together compose a wide armamentarium. The plethora of choices can, however, be clinically challenging in prescribing the most suitable treatment for any given patient. Fortunately, biomarkers can greatly facilitate the most appropriate selection. In recent years, RNA-based biomarkers have proven most promising. These molecules that range from small noncoding RNAs to protein coding gene transcripts can be valuable in cancer management and especially in cancer therapeutics. Compared to their DNA counterparts which are stable throughout treatment, RNA-biomarkers are dynamic. This allows prediction of success prior to treatment start and can identify alterations in expression that could reflect response. Moreover, improved nucleic acid technology allows RNA to be extracted from practically every biofluid/matrix and evaluated with exceedingly high analytic sensitivity. In addition, samples are largely obtained by minimally invasive procedures and as such can be used serially to assess treatment response real-time. This chapter provides the reader insight on currently known RNA biomarkers, the latest research employing Artificial Intelligence in the identification of such molecules and in clinical decisions driving forward the era of personalized oncology.
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Affiliation(s)
- Hector Katifelis
- Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Gazouli
- Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
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13
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Van Der Schueren C, Decruyenaere P, Avila Cobos F, Bult J, Deleu J, Dipalo LL, Helsmoortel HH, Hulstaert E, Morlion A, Ramos Varas E, Schoofs K, Trypsteen W, Vanden Eynde E, Van Droogenbroeck H, Verniers K, Vandesompele J, Decock A. Subpar reporting of pre-analytical variables in RNA-focused blood plasma studies. Mol Oncol 2024. [PMID: 38564603 DOI: 10.1002/1878-0261.13647] [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: 11/27/2023] [Revised: 02/13/2024] [Accepted: 03/22/2024] [Indexed: 04/04/2024] Open
Abstract
Extracellular RNA (cell-free RNA; exRNA) from blood-derived liquid biopsies is an appealing, minimally invasive source of disease biomarkers. As pre-analytical variables strongly influence exRNA measurements, their reporting is essential for meaningful interpretation and replication of results. The aim of this review was to chart to what extent pre-analytical variables are documented, to pinpoint shortcomings and to improve future reporting. In total, 200 blood plasma exRNA studies published in 2018 or 2023 were reviewed for annotation of 22 variables associated with blood collection, plasma preparation, and RNA purification. Our results show that pre-analytical variables are poorly documented, with only three out of 22 variables described in over half of the publications. The percentage of variables reported ranged from 4.6% to 54.6% (mean 24.84%) in 2023 and from 4.6% to 57.1% (mean 28.60%) in 2018. Recommendations and guidelines (i.e., BRISQ, ASCO-CAP, BloodPAC, PPMPT, and CEN standards) have currently not resulted in improved reporting. In conclusion, our results highlight the lack of reporting pre-analytical variables in exRNA studies and advocate for a consistent use of available standards, endorsed by funders and journals.
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Affiliation(s)
| | - Philippe Decruyenaere
- Department of Biomolecular Medicine, Ghent University, Belgium
- Department of Hematology, Ghent University Hospital, Belgium
| | - Francisco Avila Cobos
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
| | - Johanna Bult
- Department of Biomolecular Medicine, Ghent University, Belgium
- Department of Hematology, University Medical Center Groningen, The Netherlands
| | - Jill Deleu
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
| | - Laudonia Lidia Dipalo
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
| | - Hetty Hilde Helsmoortel
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
| | - Eva Hulstaert
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
- Department of Dermatology, AZ Sint-Blasius, Belgium
| | - Annelien Morlion
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
| | - Elena Ramos Varas
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
| | - Kathleen Schoofs
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
- Translational Oncogenomics and Bioinformatics Lab, Cancer Research Institute Ghent (CRIG), Belgium
- Center for Medical Biotechnology, VIB-UGent, Belgium
| | - Wim Trypsteen
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
| | - Eveline Vanden Eynde
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
| | - Hanne Van Droogenbroeck
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
| | - Kimberly Verniers
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
| | - Jo Vandesompele
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
- CellCarta, Belgium
| | - Anneleen Decock
- Department of Biomolecular Medicine, Ghent University, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Belgium
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Hano H, Lawrie CH, Suarez B, Paredes Lario A, Elejoste Echeverría I, Gómez Mediavilla J, Crespo Cruz MI, Lopez E, Seifert A. Power of Light: Raman Spectroscopy and Machine Learning for the Detection of Lung Cancer. ACS OMEGA 2024; 9:14084-14091. [PMID: 38559992 PMCID: PMC10975667 DOI: 10.1021/acsomega.3c09537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 02/22/2024] [Accepted: 02/27/2024] [Indexed: 04/04/2024]
Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide, emphasizing the urgent need for reliable and efficient diagnostic methods. Conventional approaches often involve invasive procedures and can be time-consuming and costly, thereby delaying the effective treatment. The current study explores the potential of Raman spectroscopy, as a promising noninvasive technique, by analyzing human blood plasma samples from lung cancer patients and healthy controls. In a benchmark study, 16 machine learning models were evaluated by employing four strategies: the combination of dimensionality reduction with classifiers; application of feature selection prior to classification; stand-alone classifiers; and a unified predictive model. The models showed different performances due to the inherent complexity of the data, achieving accuracies from 0.77 to 0.85 and areas under the curve for receiver operating characteristics from 0.85 to 0.94. Hybrid methods incorporating dimensionality reduction and feature selection algorithms present the highest figures of merit. Nevertheless, all machine learning models deliver creditable scores and demonstrate that Raman spectroscopy represents a powerful method for future in vitro diagnostics of lung cancer.
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Affiliation(s)
- Harun Hano
- CIC
nanoGUNE BRTA, 20018 San Sebastián, Spain
- Department
of Physics, University of the Basque Country
(UPV/EHU), 20018 San Sebastián, Spain
| | - Charles H. Lawrie
- IKERBASQUE—Basque
Foundation for Science, 48009 Bilbao, Spain
- Biogipuzkoa
Health Research Institute, 20014 San Sebastián, Spain
- Sino-Swiss
Institute of Advanced Technology (SSIAT), University of Shanghai, 201800 Shanghai, China
- Radcliffe
Department of Medicine, University of Oxford, OX3 9DU Oxford, U.K.
| | - Beatriz Suarez
- Faculty
of Nursing and Medicine, University of the
Basque Country (UPV/EHU), 20014 San Sebastián, Spain
- Biogipuzkoa
Health Research Institute, 20014 San Sebastián, Spain
| | - Alfredo Paredes Lario
- Servicio
de Oncología Médica, Hospital
Universitario Donostia, 20014 San Sebastián, Spain
| | | | | | | | - Eneko Lopez
- CIC
nanoGUNE BRTA, 20018 San Sebastián, Spain
- Department
of Physics, University of the Basque Country
(UPV/EHU), 20018 San Sebastián, Spain
| | - Andreas Seifert
- CIC
nanoGUNE BRTA, 20018 San Sebastián, Spain
- IKERBASQUE—Basque
Foundation for Science, 48009 Bilbao, Spain
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15
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Rong M, Zhang M, Dong F, Wu K, Cai B, Niu J, Yang L, Li Z, Lu HY. LncRNA RASAL2-AS1 promotes METTL14-mediated m6A methylation in the proliferation and progression of head and neck squamous cell carcinoma. Cancer Cell Int 2024; 24:113. [PMID: 38528591 DOI: 10.1186/s12935-024-03302-8] [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: 11/15/2023] [Accepted: 03/11/2024] [Indexed: 03/27/2024] Open
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) are key regulators of the 6-methyladenosine (m6A) epigenetic modification, playing a role in the initiation and progression of tumors. However, the regulatory mechanisms in head and neck squamous cell carcinoma (HNSCC) remain elusive. In this study, we investigated the molecular regulatory mechanisms of the lncRNA RASAL2-AS1 in the occurrence and development of HNSCC tumors. METHODS A bioinformatics analysis was conducted to analyze the expression level of RASAL2-AS1 in HNSCC and normal tissues. RASAL2-AS1 mRNA and protein levels were detected using RT-PCR and Western blotting. Wound healing, transwell assays, flow cytometry, M6A dot blot, and RNA immunoprecipitation experiments were conducted to explore the regulatory role of the RASAL2-AS1 and downstream targets METTL14/LIS1 signaling pathway in HNSCC. Immunohistochemical examination was conducted to evaluate the expression of METTL14 and LIS1 in HNSCC and normal tissues. A tumor xenograft model of BALB/c nude mice was established to assess the impact of RASAL2-AS1 on cell proliferation and growth. RESULTS RASAL2-AS1 high expression in HNSCC and cells deteriorated with survival rates of HNSCC. RASAL2-AS1 overexpression in HNSCC accelerated cell migration, colony formation, cell proliferation, cell cycle in S stage, while RASAL2-AS1 knockdown in HNSC cells inhibited cell cycle in G1 stage. After silencing METTL14, the above effects induced by overexpression of the RASAL2-AS1 were reversed. RASAL2-AS1 overexpression prompted LIS1 expression, whereas RASAL2-AS1 silencing reduced LIS1 levels in HNSCC cells, which was confirmed by immunohistological staining. Results demonstrated elevated expression of METTL14 or LIS1 in tongue cancer tissues. Overexpression of RASAL2-AS1 promoted tumor weight and tumor volume, which was counteracted by pcDNA3.1 RASAL2-AS1 plus silencing METTL14 and METTL14 and LIS1 were significantly decreased. CONCLUSION Our study highlights the functional importance of the LncRNA RASAL2-AS1 in HNSCC and might assist in the development of a prognostic stratification and therapeutic approach. Which regulates HNSCC with the dependence of m6a manner.
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Affiliation(s)
- Meiting Rong
- The Second Affiliated Hospital of Dalian Medical University, #467 Zhongshan Road, Dalian, 116023, China
- Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Ming Zhang
- The Second Affiliated Hospital of Dalian Medical University, #467 Zhongshan Road, Dalian, 116023, China
| | - Feihong Dong
- The Second Affiliated Hospital of Dalian Medical University, #467 Zhongshan Road, Dalian, 116023, China
| | - Ke Wu
- The Second Affiliated Hospital of Dalian Medical University, #467 Zhongshan Road, Dalian, 116023, China
| | - Bingkun Cai
- The Second Affiliated Hospital of Dalian Medical University, #467 Zhongshan Road, Dalian, 116023, China
| | - Jinrui Niu
- The Second Affiliated Hospital of Dalian Medical University, #467 Zhongshan Road, Dalian, 116023, China
| | - Le Yang
- The Second Affiliated Hospital of Dalian Medical University, #467 Zhongshan Road, Dalian, 116023, China
| | - Zhongyan Li
- The Second Affiliated Hospital of Dalian Medical University, #467 Zhongshan Road, Dalian, 116023, China.
| | - Hui-Yi Lu
- The Second Affiliated Hospital of Dalian Medical University, #467 Zhongshan Road, Dalian, 116023, China.
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16
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Kim YJ, Rho WY, Park SM, Jun BH. Optical nanomaterial-based detection of biomarkers in liquid biopsy. J Hematol Oncol 2024; 17:10. [PMID: 38486294 PMCID: PMC10938695 DOI: 10.1186/s13045-024-01531-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 03/02/2024] [Indexed: 03/18/2024] Open
Abstract
Liquid biopsy, which is a minimally invasive procedure as an alternative to tissue biopsy, has been introduced as a new diagnostic/prognostic measure. By screening disease-related markers from the blood or other biofluids, it promises early diagnosis, timely prognostication, and effective treatment of the diseases. However, there will be a long way until its realization due to its conceptual and practical challenges. The biomarkers detected by liquid biopsy, such as circulating tumor cell (CTC) and circulating tumor DNA (ctDNA), are extraordinarily rare and often obscured by an abundance of normal cellular components, necessitating ultra-sensitive and accurate detection methods for the advancement of liquid biopsy techniques. Optical biosensors based on nanomaterials open an important opportunity in liquid biopsy because of their enhanced sensing performance with simple and practical properties. In this review article, we summarized recent innovations in optical nanomaterials to demonstrate the sensitive detection of protein, peptide, ctDNA, miRNA, exosome, and CTCs. Each study prepares the optical nanomaterials with a tailored design to enhance the sensing performance and to meet the requirements of each biomarker. The unique optical characteristics of metallic nanoparticles (NPs), quantum dots, upconversion NPs, silica NPs, polymeric NPs, and carbon nanomaterials are exploited for sensitive detection mechanisms. These recent advances in liquid biopsy using optical nanomaterials give us an opportunity to overcome challenging issues and provide a resource for understanding the unknown characteristics of the biomarkers as well as the mechanism of the disease.
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Affiliation(s)
- Young Jun Kim
- Department of Bioscience and Biotechnology, Konkuk University, Seoul, 05029, Republic of Korea
| | - Won-Yeop Rho
- School of International Engineering and Science, Jeonbuk National University, Chonju, 54896, Republic of Korea
| | - Seung-Min Park
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, 637459, Singapore.
| | - Bong-Hyun Jun
- Department of Bioscience and Biotechnology, Konkuk University, Seoul, 05029, Republic of Korea.
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17
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Elkahwagy DM, Kiriacos CJ, Sobeih ME, Khorshid OMR, Mansour M. The lncRNAs Gas5, MALAT1 and SNHG8 as diagnostic biomarkers for epithelial malignant pleural mesothelioma in Egyptian patients. Sci Rep 2024; 14:4823. [PMID: 38413635 PMCID: PMC10899637 DOI: 10.1038/s41598-024-55083-9] [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: 01/24/2024] [Accepted: 02/20/2024] [Indexed: 02/29/2024] Open
Abstract
Long noncoding RNAs have been shown to be involved in a myriad of physiological and pathological pathways. To date, malignant pleural mesothelioma (MPM) is considered an extremely aggressive cancer. One reason for this is the late diagnosis of the disease, which can occur within 30-40 years of asbestos exposure. There is an immense need for the development of new, sensitive, inexpensive and easy methods for the early detection of this disease other than invasive methods such as biopsy. The aim of this study was to determine the expression of circulating lncRNAs in mesothelioma patient plasma to identify potential biomarkers. Ten previously identified lncRNAs that were shown to be aberrantly expressed in mesothelioma tissues were selected as candidates for subsequent validation. The expression of the ten selected candidate lncRNAs was verified via quantitative PCR (qPCR) in human plasma samples from mesothelioma patients versus healthy controls. The expression levels of circulating GAS5, SNHG8 and MALAT1 were significantly greater in plasma samples from patients than in those from controls. The ROC analysis of both MALAT1 and SNHG8 revealed 88.89% sensitivity and 66.67% specificity. The sensitivity of these markers was greater than that of GAS5 (sensitivity 72.22% and specificity 66.67%). The regression model for GAS5 was statistically significant, while that for SNHG8 and MALAT1 was not significant due to the small sample size. The area under the curve (AUC) of the three ROC curves was acceptable and significant: 0.7519 for GAS5, 0.7352 for SNHG8 and 0.7185 for MALAT1. This finding confirmed their ability to be used as markers. The three lncRNAs were not affected by age, sex or smoking status. The three lncRNAs showed great potential as independent predictive diagnostic biomarkers. Although the prediction model for MALAT1 did not significantly differ, MALAT1 was significantly expressed in patients more than in controls (p = 0.0266), and the recorded sensitivity and specificity were greater than those of GAS5.
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Affiliation(s)
- Dina Mohamed Elkahwagy
- Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, 11835, Egypt
| | - Caroline Joseph Kiriacos
- Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, 11835, Egypt
| | - Mohamed Emam Sobeih
- Department of Medical Oncology, National Cancer Institute, NCI, Cairo University, Cairo, Egypt
| | - Ola M Reda Khorshid
- Department of Medical Oncology, National Cancer Institute, NCI, Cairo University, Cairo, Egypt
| | - Manar Mansour
- Pharmaceutical Biology and Microbiology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.
- Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, 11835, Egypt.
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18
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Dybiec J, Frąk W, Kućmierz J, Tokarek J, Wojtasińska A, Młynarska E, Rysz J, Franczyk B. Liquid Biopsy: A New Avenue for the Diagnosis of Kidney Disease: Diabetic Kidney Disease, Renal Cancer, and IgA Nephropathy. Genes (Basel) 2024; 15:78. [PMID: 38254967 PMCID: PMC10815875 DOI: 10.3390/genes15010078] [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: 12/10/2023] [Revised: 01/03/2024] [Accepted: 01/05/2024] [Indexed: 01/24/2024] Open
Abstract
Kidney diseases are some of the most common healthcare problems. As the population of elderly individuals with concurrent health conditions continues to rise, there will be a heightened occurrence of these diseases. Due to the renal condition being one of the longevity predictors, early diagnosis of kidney dysfunction plays a crucial role. Currently, prevalent diagnostic tools include laboratory tests and kidney tissue biopsies. New technologies, particularly liquid biopsy and new detection biomarkers, hold promise for diagnosing kidney disorders. The aim of this review is to present modern diagnostic methods for kidney diseases. The paper focuses on the advances in diagnosing three common renal disorders: diabetic kidney disease, renal cancer, and immunoglobulin A nephropathy. We highlight the significance of liquid biopsy and epigenetic changes, such as DNA methylation, microRNA, piRNAs, and lncRNAs expression, or single-cell transcriptome sequencing in the assessment of kidney diseases. This review underscores the importance of early diagnosis for the effective management of kidney diseases and investigates liquid biopsy as a promising approach.
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Affiliation(s)
- Jill Dybiec
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Weronika Frąk
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Joanna Kućmierz
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Julita Tokarek
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Armanda Wojtasińska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
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19
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Bagheri R, Ghorbian M, Ghorbian S. Tumor circulating biomarkers in colorectal cancer. Cancer Treat Res Commun 2023; 38:100787. [PMID: 38194840 DOI: 10.1016/j.ctarc.2023.100787] [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: 11/03/2023] [Revised: 12/11/2023] [Accepted: 12/21/2023] [Indexed: 01/11/2024]
Abstract
CRC is a major global health concern and is responsible for a significant number of cancer-related deaths each year. The successful treatment of CRC becomes more difficult when it goes undetected until it has advanced to a later stage. Diagnostic biomarkers can play a critical role in the early detection of CRC, which leads to improved patient outcomes and increased survival rates. It is important to develop reliable biomarkers for the early detection of CRC to enable timely diagnosis and treatment. To date, CRC detection methods such as endoscopy, blood, and stool tests are imperfect and often only identify cases in the later stages of the disease. To overcome these limitations, researchers are turning to molecular biomarkers as a promising avenue for improving CRC detection. Diagnostic information can be provided more reliably through a noninvasive approach using biomarkers such as mRNA, circulating cell-free DNA, micro-RNA, long non-coding RNA, and proteins. These biomarkers can be found in blood, tissue, feces, and volatile organic compounds. The identification of molecular biomarkers with high sensitivity and specificity for early detection of CRC that are safe, cost-effective, and easily measurable remains a significant challenge for researchers. In this article, we will explore the latest advancements in blood-based diagnostic biomarkers for CRC and their potential impact on improving patient survival rates.
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Affiliation(s)
- Raana Bagheri
- Department of Molecular Genetics, Ahar Branch, Islamic Azad University, Ahar, Iran
| | - Mohsen Ghorbian
- Department of Computer Engineering, Qom Branch, Islamic Azad University, Qom, Iran
| | - Saeid Ghorbian
- Department of Molecular Genetics, Ahar Branch, Islamic Azad University, Ahar, Iran.
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20
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Mohammed EM. Circular RNA in Multiple Sclerosis: Pathogenicity and Potential Biomarker Development: A Systematic Review. Epigenet Insights 2023; 16:25168657231213195. [PMID: 38033465 PMCID: PMC10687999 DOI: 10.1177/25168657231213195] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 10/24/2023] [Indexed: 12/02/2023] Open
Abstract
Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS that affects millions of people worldwide. The causes of the disease remain unknown despite extensive efforts to understand it. CircRNAs are a unique class of endogenous non-coding RNA that are abundant, stable, conserved, and specifically expressed molecules, making them a promising biomarker of diseases. This review investigates the role of circRNA in MS pathogenicity and their potential as a biomarker through a comprehensive literature search conducted in 8 scientific databases. The studies found that there are differentially expressed circRNAs in MS patients compared to healthy controls (HC), and this difference is even more pronounced in different MS subtypes. Enrichment of circRNAs in linkage disequilibrium (LD) blocks that harbor MS-associated SNPs suggests that these SNPs manipulate the levels of circRNAs in the surrounding area, contributing to disease pathogenicity. While circRNA shows promise as an indicator or biomarker for MS disease pathology, further research is needed to fully explore its potential and impact on human biology.
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Affiliation(s)
- Eiman M Mohammed
- Kuwait Cancer Control Centre, Medical Laboratory Department, Molecular Genetics Laboratory, Ministry of Health, Shuwaikh, Kuwait
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21
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Akshaya RL, Saranya I, Selvamurugan N. MicroRNAs mediated interaction of tumor microenvironment cells with breast cancer cells during bone metastasis. Breast Cancer 2023; 30:910-925. [PMID: 37578597 DOI: 10.1007/s12282-023-01491-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 08/07/2023] [Indexed: 08/15/2023]
Abstract
Breast cancer (BC) bone metastasis is primarily osteolytic and has limited therapeutic options. Metastasized BC cells prime the secondary environment in bone by forming a tumor niche, which favors their homing and colonization. The tumor microenvironment (TME) is primarily generated by the cancer cells. Bone TME is an intricate network of multiple cells, including altered bone, tumor, stromal, and immune cells. Recent findings highlight the significance of small non-coding microRNAs (miRNAs) in influencing TME during tumor metastasis. MiRNAs from TME-resident cells facilitate the interaction between the tumor and its microenvironment, thereby regulating the biological processes of tumors. These miRNAs can serve as oncogenes or tumor suppressors. Hence, both miRNA inhibitors and mimics are extensively utilized in pre-clinical trials for modulating the phenotypes of tumor cells and associated stromal cells. This review briefly summarizes the recent developments on the functional role of miRNAs secreted directly or indirectly from the TME-resident cells in facilitating tumor growth, progression, and metastasis. This information would be beneficial in developing novel targeted therapies for BC.
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Affiliation(s)
- R L Akshaya
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603 103, Tamil Nadu, India
| | - I Saranya
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603 103, Tamil Nadu, India
| | - N Selvamurugan
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603 103, Tamil Nadu, India.
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22
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Decruyenaere P, Giuili E, Verniers K, Anckaert J, De Grove K, Van der Linden M, Deeren D, Van Dorpe J, Offner F, Vandesompele J. Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies. Front Oncol 2023; 13:1221471. [PMID: 37954086 PMCID: PMC10634215 DOI: 10.3389/fonc.2023.1221471] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 09/18/2023] [Indexed: 11/14/2023] Open
Abstract
Introduction Diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) are aggressive histological subtypes of non-Hodgkin's lymphoma. Improved understanding of the underlying molecular pathogenesis has led to new classification and risk stratification tools, including the development of cell-free biomarkers through liquid biopsies. The goal of this study was to investigate cell-free RNA (cfRNA) biomarkers in DLBCL and PMBCL patients. Materials and methods Blood plasma samples (n=168) and matched diagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples (n=69) of DLBCL patients, PMBCL patients and healthy controls were collected between 2016-2021. Plasma samples were collected at diagnosis, at interim evaluation, after treatment, and in case of refractory or relapsed disease. RNA was extracted from 200 µl plasma using the miRNeasy serum/plasma kit and from FFPE tissue using the miRNeasy FFPE kit. RNA was subsequently sequenced on a NovaSeq 6000 instrument using the SMARTer Stranded Total RNA-seq pico v3 library preparation kit. Results Higher cfRNA concentrations were demonstrated in lymphoma patients compared to healthy controls. A large number of differentially abundant genes were identified between the cell-free transcriptomes of DLBCL patients, PMBCL patients, and healthy controls. Overlap analyses with matched FFPE samples showed that blood plasma has a unique transcriptomic profile that significantly differs from that of the tumor tissue. As a good concordance between tissue-derived gene expression and the immunohistochemistry Hans algorithm for cell-of-origin (COO) classification was demonstrated in the FFPE samples, but not in the plasma samples, a 64-gene cfRNA classifier was developed that can accurately determine COO in plasma. High plasma levels of a 9-gene signature (BECN1, PRKCB, COPA, TSC22D3, MAP2K3, UQCRHL, PTMAP4, EHD1, NAP1L1 pseudogene) and a 5-gene signature (FTH1P7, PTMAP4, ATF4, FTH1P8, ARMC7) were significantly associated with inferior progression-free and overall survival in DLBCL patients, respectively, independent of the NCCN-IPI score. Conclusion Total RNA sequencing of blood plasma samples allows the analysis of the cell-free transcriptome in DLBCL and PMBCL patients and demonstrates its unexplored potential in identifying diagnostic, cell-of-origin, and prognostic cfRNA biomarkers.
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Affiliation(s)
- Philippe Decruyenaere
- Department of Hematology, Ghent University Hospital, Ghent, Belgium
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium
- Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
| | - Edoardo Giuili
- Interuniversity Institute of Bioinformatics in Brussels (IB), Free University of Brussels, Brussels, Belgium
- Department of Biotechnology and Pharmacy, University of Bologna, Bologna, Italy
| | - Kimberly Verniers
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium
- Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
| | - Jasper Anckaert
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium
- Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
| | - Katrien De Grove
- Department of Hematology, Ghent University Hospital, Ghent, Belgium
| | | | - Dries Deeren
- Department of Hematology, Algemeen Ziekenhuis (AZ) Delta Roeselare-Menen, Roeselare, Belgium
| | - Jo Van Dorpe
- Department of Pathology, Ghent University Hospital, Ghent, Belgium
| | - Fritz Offner
- Department of Hematology, Ghent University Hospital, Ghent, Belgium
| | - Jo Vandesompele
- OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium
- Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
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Fan X, Huang Y, Zhong Y, Yan Y, Li J, Fan Y, Xie F, Luo Q, Zhang Z. A new marker constructed from immune-related lncRNA pairs can be used to predict clinical treatment effects and prognosis: in-depth exploration of underlying mechanisms in HNSCC. World J Surg Oncol 2023; 21:250. [PMID: 37592311 PMCID: PMC10433616 DOI: 10.1186/s12957-023-03066-x] [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: 03/18/2022] [Accepted: 06/04/2023] [Indexed: 08/19/2023] Open
Abstract
BACKGROUND Long non-coding RNA (lncRNA) plays a vital role in tumor proliferation, migration, and treatment. Since it is challenging to standardize the gene expression levels detected by different platforms, the signatures composed of many immune-related single lncRNAs are still inaccurate. Utilizing a gene pair formed of two immune-related lncRNAs and strategically assigning values can effectively meet the demand for a higher-accuracy dual biomarker combination. METHODS Co-expression and differential expression analyses were performed on immune genes and lncRNAs data from The Cancer Genome Atlas and the ImmPort database to obtain differentially expressed immune-related lncRNAs for pairwise pairing. The prognostic-related differentially expressed immune-related lncRNAs (PR-DE-irlncRNAs) pairs were then identified by univariate Cox regression and used for lasso regression to construct a prognostic model. Various methods were used to validate the predictive prognostic performance of the model. Additionally, we explored the potential guiding value of the model in immunotherapy and chemotherapy and constructed a nomogram suitable for efficient prognosis prediction. Mechanistic exploration of anti-tumor immunity and mutational perspectives are also included. We also analyzed the correlation between the model and immune checkpoint inhibitors (ICIs)-related, N6-methyadenosine (m6A)-related, and multidrug resistance genes. RESULTS We used a total of 20 pairs of PR-DE-irlncRNAs to create a prognosis model. Quantitative real-time polymerase chain reaction experiments further verified the abnormal expression of 11 lncRNAs in HNSCC cells. Various methods have confirmed the excellent performance of the model in predicting patient prognosis. We reasoned that lncRNAs/TP53 mutation might play a positive/negative anti-tumor role through the immune system by multi-perspective analyses. Finally, it was found that the prognostic model was closely related to immunotherapy and chemotherapy as well as the expression of ICIs/m6A/multidrug resistance-related genes. CONCLUSION The prognostic model performs excellently in predicting the prognosis of patients and provides the potential value of practical guidance for treatment.
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Affiliation(s)
- Xin Fan
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Yuhan Huang
- Yunnan University of Chinese Medicine, Kunming, Yunnan Province, China
| | - Yun Zhong
- The First Clinical Medical College of Nanchang University, Nanchang, Jiangxi Province, China
| | - Yujie Yan
- School of Stomatology, Nanchang University, Nanchang, Jiangxi Province, China
| | - Jiaqi Li
- School of Stomatology, Nanchang University, Nanchang, Jiangxi Province, China
| | - Yanting Fan
- The First Clinical Medical College of Nanchang University, Nanchang, Jiangxi Province, China
| | - Fei Xie
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Qing Luo
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Zhiyuan Zhang
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
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Kan CM, Pei XM, Yeung MHY, Jin N, Ng SSM, Tsang HF, Cho WCS, Yim AKY, Yu ACS, Wong SCC. Exploring the Role of Circulating Cell-Free RNA in the Development of Colorectal Cancer. Int J Mol Sci 2023; 24:11026. [PMID: 37446204 PMCID: PMC10341751 DOI: 10.3390/ijms241311026] [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: 05/21/2023] [Revised: 06/25/2023] [Accepted: 07/02/2023] [Indexed: 07/15/2023] Open
Abstract
Circulating tumor RNA (ctRNA) has recently emerged as a novel and attractive liquid biomarker. CtRNA is capable of providing important information about the expression of a variety of target genes noninvasively, without the need for biopsies, through the use of circulating RNA sequencing. The overexpression of cancer-specific transcripts increases the tumor-derived RNA signal, which overcomes limitations due to low quantities of circulating tumor DNA (ctDNA). The purpose of this work is to present an up-to-date review of current knowledge regarding ctRNAs and their status as biomarkers to address the diagnosis, prognosis, prediction, and drug resistance of colorectal cancer. The final section of the article discusses the practical aspects involved in analyzing plasma ctRNA, including storage and isolation, detection technologies, and their limitations in clinical applications.
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Affiliation(s)
- Chau-Ming Kan
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China; (C.-M.K.); (H.F.T.)
| | - Xiao Meng Pei
- Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR, China; (X.M.P.); (M.H.Y.Y.)
| | - Martin Ho Yin Yeung
- Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR, China; (X.M.P.); (M.H.Y.Y.)
| | - Nana Jin
- Codex Genetics Limited, Shatin, Hong Kong SAR, China; (N.J.); (A.K.-Y.Y.); (A.C.-S.Y.)
| | - Simon Siu Man Ng
- Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China;
| | - Hin Fung Tsang
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China; (C.-M.K.); (H.F.T.)
| | - William Chi Shing Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong SAR, China;
| | - Aldrin Kay-Yuen Yim
- Codex Genetics Limited, Shatin, Hong Kong SAR, China; (N.J.); (A.K.-Y.Y.); (A.C.-S.Y.)
| | - Allen Chi-Shing Yu
- Codex Genetics Limited, Shatin, Hong Kong SAR, China; (N.J.); (A.K.-Y.Y.); (A.C.-S.Y.)
| | - Sze Chuen Cesar Wong
- Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR, China; (X.M.P.); (M.H.Y.Y.)
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Guo X, Zhang Y, Zhang Z, Lu L, Liu Y, Li Z, Zhou T, Zhang J, Li W, You W, Tao G, Chen W, Zeng H, Pan K. Gastric cancer-associated long non-coding RNA profiling and noninvasive biomarker screening based on a high-risk population cohort. Cancer Med 2023. [PMID: 37084181 DOI: 10.1002/cam4.5905] [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: 01/17/2023] [Revised: 03/10/2023] [Accepted: 03/23/2023] [Indexed: 04/22/2023] Open
Abstract
BACKGROUND Effective noninvasive biomarkers of gastric cancer (GC) are critical for early detection and improvement of prognosis. We performed genome-wide long non-coding RNA (lncRNA) microarray analysis to identify and validate novel GC biomarkers depending on a high-risk population cohort. METHODS LncRNA profiles were described using the Human LncRNA Microarray between GC and control plasma samples. The differential candidate lncRNAs were validated in two stages by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We further evaluated the joint effect between the GC-associated lncRNA and Helicobacter pylori (H. pylori) infection on the risk of cardia and non-cardia GC, respectively. RESULTS Different lncRNA expression profiles were identified between GC and control plasma with a total of 1206 differential lncRNAs including 470 upregulated and 736 downregulated in GC compared with the control group. The eight significantly upregulated lncRNAs (RP11-521D12.1, AC011995.3, RP11-5P4.3, RP11-244 K5.6, RP11-422 J15.1, CTD-2306 M5.1, CTC-428G20.2, and AC009133.20) in GC cases both in the present study and a similar microarray screening study by our collaborative team were selected for a two-stage validation. After the large sample size validation, the subjects with higher expression of RP11-244 K5.6 showed a significantly increased risk of GC with an adjusted odds ratio (OR) as 2.68 and 95% confidence interval (CI) as 1.15-6.24. Joint effects between RP11-244 K5.6 expression and H. pylori infection on the risk of GC were evaluated with no statistical significance. CONCLUSIONS Our study found different lncRNA expression profiles between GC and control plasma and preliminarily identified RP11-244 K5.6 as a potential noninvasive biomarker for GC screening.
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Affiliation(s)
- Xiaoying Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University School of Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yang Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University School of Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhiyi Zhang
- Department of Gastroenterology, Gansu Wuwei Tumor Hospital, Wuwei, China
| | - Linzhi Lu
- Department of Gastroenterology, Gansu Wuwei Tumor Hospital, Wuwei, China
| | - Yuqin Liu
- Cancer Epidemiology Research Center, Gansu Provincial Cancer Hospital, Lanzhou, China
| | - Zhexuan Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University School of Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Tong Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University School of Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jingying Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University School of Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wenqing Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University School of Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Weicheng You
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University School of Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Guoquan Tao
- Department of General Surgery, The Affiliated Huai'an No.1 People's Hospital, Nanjing Medical University, Huai'an, 223300, China
| | - Wanqing Chen
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hongmei Zeng
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Kaifeng Pan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University School of Oncology, Peking University Cancer Hospital & Institute, Beijing, China
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Li P, Mi Q, Yan S, Xie Y, Cui Z, Zhang S, Wang Y, Gao H, Wang Y, Li J, Du L, Wang C. Characterization of circSCL38A1 as a novel oncogene in bladder cancer via targeting ILF3/TGF-β2 signaling axis. Cell Death Dis 2023; 14:59. [PMID: 36697384 PMCID: PMC9876890 DOI: 10.1038/s41419-023-05598-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 01/12/2023] [Accepted: 01/16/2023] [Indexed: 01/26/2023]
Abstract
The regulatory role of circRNAs in cancer metastasis has become a focused issue in recent years. To date, however, the discovery of novel functional circRNAs and their regulatory mechanisms via binding with RBPs in bladder cancer (BC) are still lacking. Here, we screened out circSLC38A1 based on our sequencing data and followed validation with clinical tissue samples and cell lines. Functional assays showed that circSLC38A1 promoted BC cell invasion in vitro and lung metastasis of mice in vivo. By conducting RNA pull-down, mass spectrum, and RIP assays, circSLC38A1 was found to interact with Interleukin enhancer-binding factor 3 (ILF3), and stabilize ILF3 protein via modulating the ubiquitination process. By integrating our CUT&Tag-seq and RNA-seq data, TGF-β2 was identified as the functional target of the circSLC38A1-ILF3 complex. In addition, m6A methylation was enriched in circSLC38A1 and contributed to its upregulation. Clinically, circSLC38A1 was identified in serum exosomes of BC patients and could distinguish BC patients from healthy individuals with a diagnostic accuracy of 0.878. Thus, our study revealed an essential role and clinical significance of circSLC38A1 in BC via activating the transcription of TGF-β2 in an ILF3-dependent manner, extending the understanding of the importance of circRNA-mediated transcriptional regulation in BC metastasis.
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Affiliation(s)
- Peilong Li
- Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China
- Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, Shandong, China
| | - Qi Mi
- Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China
| | - Suzhen Yan
- Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China
- Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, Shandong, China
| | - Yan Xie
- Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China
| | - Zilian Cui
- Department of Urology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
| | - Shujun Zhang
- Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China
| | - Yifan Wang
- Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China
| | - Huiru Gao
- Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China
| | - Yunshan Wang
- Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China
- Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, Shandong, China
- Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, Shandong, China
| | - Juan Li
- Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China.
- Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, Shandong, China.
| | - Lutao Du
- Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China.
- Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, Shandong, China.
- Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, Shandong, China.
| | - Chuanxin Wang
- Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China.
- Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, Shandong, China.
- Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, Shandong, China.
- Shandong Technology Innovation Center for Big Data and Precision Medicine of Cancer, Jinan, 250033, Shandong, China.
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Li W, Gonzalez-Gonzalez M, Sanz-Criado L, Garcia-Carbonero N, Celdran A, Villarejo-Campos P, Minguez P, Pazo-Cid R, Garcia-Jimenez C, Orta-Ruiz A, Garcia-Foncillas J, Martinez-Useros J. A Novel PiRNA Enhances CA19-9 Sensitivity for Pancreatic Cancer Identification by Liquid Biopsy. J Clin Med 2022; 11:7310. [PMID: 36555927 PMCID: PMC9784851 DOI: 10.3390/jcm11247310] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 12/01/2022] [Accepted: 12/07/2022] [Indexed: 12/13/2022] Open
Abstract
Pancreatic cancer is one of the deadliest tumours worldwide, and its poor prognosis is due to an inability to detect the disease at the early stages, thereby creating an urgent need to develop non-invasive biomarkers. P-element-induced wimpy testis (PIWI) proteins work together with piwi-interacting RNAs (piRNAs) to perform epigenetic regulation and as such hold great potential as biomarkers for pancreatic cancer. PIWIL2 and PIWIL4 are associated with better prognosis, while PIWIL1 and PIWIL3 involvement appears to be associated with carcinogenesis. We aimed to discover PIWIL3- and PIWIL4-modulated piRNAs and determine their potential mechanisms in pancreatic cancer and the clinical implications. PIWIL3 or PIWIL4 was downregulated in pancreatic cancer-derived cell lines or in a non-tumour cell line. Differentially expressed piRNAs were analysed by next generation sequencing of small RNA. Nine fresh-frozen samples from solid human pancreases (three healthy pancreases, three intraductal papillary mucinous neoplasms, and three early-stage pancreatic cancers) were included in the sequencing analysis. Two piRNAs associated with PIWIL3 (piR-168112 and piR-162725) were identified in the neoplastic cells; in untransformed samples, we identified one piRNA associated with PIWIL4 (pir-366845). After validation in pancreatic cancer-derived cell lines and one untransformed pancreatic cell line, these piRNAs were evaluated in plasma samples from healthy donors (n = 27) or patients with pancreatic cancer (n = 45). Interestingly, piR-162725 expression identified pancreatic cancer patients versus healthy donors in liquid biopsies. Moreover, the potential of the serum carbohydrate antigen 19-9 (CA19-9) biomarker to identify pancreatic cancer patients was greatly enhanced when combined with piR-162725 detection. The enhanced diagnostic potential for the early detection of pancreatic cancer in liquid biopsies of these new small non-coding RNAs will likely improve the prognosis and management of this deadly cancer.
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Affiliation(s)
- Weiyao Li
- Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510085, China
| | | | - Lara Sanz-Criado
- Translational Oncology Division, OncoHealth Institute, Health Research Institute Fundacion Jimenez Diaz, Fundacion Jimenez Diaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain
| | - Nuria Garcia-Carbonero
- Translational Oncology Division, OncoHealth Institute, Health Research Institute Fundacion Jimenez Diaz, Fundacion Jimenez Diaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain
| | - Angel Celdran
- General and Hepatobiliary Surgery Unit, Fundacion Jimenez Diaz University Hospital, 28040 Madrid, Spain
| | - Pedro Villarejo-Campos
- General and Hepatobiliary Surgery Unit, Fundacion Jimenez Diaz University Hospital, 28040 Madrid, Spain
| | - Pablo Minguez
- Genetics and Genomics Department, IIS-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid (IIS-FJD, UAM), Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Bioinformatics Unit, IIS-FJD, UAM, 28040 Madrid, Spain
| | - Roberto Pazo-Cid
- Department of Medical Oncology, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
| | - Custodia Garcia-Jimenez
- Area of Physiology, Department of Basic Health Sciences, Faculty of Health Sciences, Rey Juan Carlos University, 28922 Madrid, Spain
| | - Alberto Orta-Ruiz
- Department of Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), CIBERONC, 28040 Madrid, Spain
- Department of Medical Oncology, MD Anderson Cancer Center Madrid, 28033 Madrid, Spain
- Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223 Pozuelo de Alarcón, Spain
| | - Jesus Garcia-Foncillas
- Translational Oncology Division, OncoHealth Institute, Health Research Institute Fundacion Jimenez Diaz, Fundacion Jimenez Diaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain
| | - Javier Martinez-Useros
- Translational Oncology Division, OncoHealth Institute, Health Research Institute Fundacion Jimenez Diaz, Fundacion Jimenez Diaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain
- Area of Physiology, Department of Basic Health Sciences, Faculty of Health Sciences, Rey Juan Carlos University, 28922 Madrid, Spain
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Zhao X, Dong R, Tang Z, Wang J, Wang C, Song Z, Ni B, Zhang L, He X, You Y. Circular RNA circLOC101928570 suppresses systemic lupus erythematosus progression by targeting the miR-150-5p/c-myb axis. J Transl Med 2022; 20:547. [DOI: 10.1186/s12967-022-03748-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 11/02/2022] [Indexed: 11/28/2022] Open
Abstract
Abstract
Background
Accumulating evidence supports the implication of circular RNAs (circRNAs) in systemic lupus erythematosus (SLE). However, little is known about the detailed mechanisms and roles of circRNAs in the pathogenesis of SLE.
Methods
Quantitative real-time PCR was used to determine the levels of circLOC101928570 and miR-150-5p in peripheral blood mononuclear cells of SLE. Overexpression and knockdown experiments were conducted to assess the effects of circLOC101928570. Fluorescence in situ hybridization, RNA immunoprecipitation, luciferase reporter assays, Western blot, flow cytometry analysis and enzyme-linked immunosorbent assay were used to investigate the molecular mechanisms underlying the function of circLOC101928570.
Results
The results showed that the level of circLOC101928570 was significantly downregulated in SLE and correlated with the systemic lupus erythematosus disease activity index. Functionally, circLOC101928570 acted as a miR-150-5p sponge to relieve the repressive effect on its target c-myb, which modulates the activation of immune inflammatory responses. CircLOC101928570 knockdown enhanced apoptosis. Moreover, circLOC101928570 promoted the transcriptional level of IL2RA by directly regulating the miR-150-5p/c-myb axis.
Conclusion
Overall, our findings demonstrated that circLOC101928570 played a critical role in SLE. The downregulation of circLOC101928570 suppressed SLE progression through the miR-150-5p/c-myb/IL2RA axis. Our findings identified that circLOC101928570 serves as a potential biomarker for the diagnosis and therapy of SLE.
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Xie Q, Zhang D, Ye H, Wu Z, Sun Y, Shen H. Identification of key snoRNAs serves as biomarkers for hepatocellular carcinoma by bioinformatics methods. Medicine (Baltimore) 2022; 101:e30813. [PMID: 36181013 PMCID: PMC9524901 DOI: 10.1097/md.0000000000030813] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a common malignancy with high mortality and poor prognosis due to a lack of predictive markers. However, research on small nuclear RNAs (snoRNAs) in HCC were very little. This study aimed to identify a potential diagnostic and prognostic snoRNA signature for HCC. METHODS HCC datasets from the cancer genome atlas (TCGA) and international cancer genome consortium (ICGC) cohorts were used. Differentially expressed snoRNA (DEs) were identified using the limma package. Based on the DEs, diagnostic and prognostic models were established by the least absolute shrinkage and selection operator (LASSO) regression and COX analysis, and Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curve analysis were conducted to evaluate the efficiency of signatures. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to analyze the risk score and further explore the potential correlation between the risk groups and tumor immune status in TCGA. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the functions of key snoRNAs. RESULTS We constructed a 6-snoRNAs signature which could classify patients into high- or low-risk groups and found that patients in the high-risk group had a worse prognosis than those in the low-risk group and were significantly involved in p53 processes. Tumor immune status analysis revealed that CTLA4 and PDCD1 (PD1) were highly expressed in the high-risk group, which responded to PD1 inhibitor therapy. Additionally, a 25-snoRNAs diagnostic signature was constructed with an area under the curve (AUC) of 0.933 for distinguishing HCCs from normal controls. Finally, 3 key snoRNAs (SNORA11, SNORD124, and SNORD46) were identified with both diagnostic and prognostic efficacy, some of which were closely related to the spliceosome and Notch signaling pathways. CONCLUSIONS Our study identified 6 snoRNAs that may serve as novel prognostic models and 3 key snoRNAs with both diagnostic and prognostic efficacy for HCC.
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Affiliation(s)
- Qingqing Xie
- Department of Clinical Laboratory, Third Affiliated Hospital of Guangxi University of Chinese Medicine, Liuzhou, Guangxi, China
| | - Di Zhang
- Department of Clinical Laboratory, The Third Xiangya Hospital of Central South University, Hunan, China
| | - Huifeng Ye
- Department of Clinical Laboratory, Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People’s Hospital, Guigang, Guangxi, China
| | - Zhitong Wu
- Department of Clinical Laboratory, Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People’s Hospital, Guigang, Guangxi, China
| | - Yifan Sun
- Department of Clinical Laboratory, Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People’s Hospital, Guigang, Guangxi, China
| | - Haoming Shen
- Department of Clinical Laboratory, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan, China
- *Correspondence: Haoming Shen, Department of Clinical Laboratory, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Xianjia Lake Street 410031, Changsha, Hunan, China (e-mail: )
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Wen G, Gu W. Circular RNAs in peripheral blood mononuclear cells are more stable than linear RNAs upon sample processing delay. J Cell Mol Med 2022; 26:5021-5032. [PMID: 36039821 PMCID: PMC9549506 DOI: 10.1111/jcmm.17525] [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: 04/17/2022] [Revised: 08/06/2022] [Accepted: 08/11/2022] [Indexed: 12/01/2022] Open
Abstract
Circular RNAs (circRNAs) are a novel class of RNAs with closed loop structure. Blood circRNAs are widely acknowledged to be more stable than linear mRNAs, which show promising prospect to be liquid biopsy biomarkers for clinical applications. However, accumulating studies have demonstrated that sample processing delays have profound effects on blood transcriptome expression profiles, wherein knowledge remains elusive about the impacts of prolonged sample processing on blood expression profiles of circRNAs. We collected whole blood samples from three donors and isolated peripheral blood mononuclear cells (PBMCs) at six different incubation time points. We measured total RNA expression profiles using RNA sequencing (RNA‐seq) and investigated the differentially expressed circRNAs, mRNAs and lncRNAs upon blood processing delay. Meanwhile, we explored the underlying inducement of aberrant expression of circRNAs against their corresponding mRNA transcripts. Finally, we utilized rMATS‐turbo and CIRI‐AS, respectively, to screen out differential alternative splicing (AS) events in linear mRNAs and circRNAs. Sample incubation at 4°C lasting to 48 hours (h) led to minimal effects to circRNAs' expression. However, it induced extensive alterations for mRNAs and lncRNAs when the incubation time was beyond 12 h. Additionally, only 2 h processing delays may result in profound impacts on AS events of linear mRNAs, while less impact on the equivalence of circRNAs. Our results suggested that PBMC circRNAs are stable upon sample processing delay, which are more suitable to be liquid biopsy biomarkers.
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Affiliation(s)
- Guoxia Wen
- State Key Laboratory of Bioelectronics, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, China
| | - Wanjun Gu
- Collaborative Innovation Center of Jiangsu Province of Cancer Prevention and Treatment of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.,School of Artificial Intelligence and Information Technology, Nanjing University of Chinese Medicine, Nanjing, China
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31
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Ahmad E, Ali A, Nimisha, Kumar Sharma A, Apurva, Kumar A, Dar GM, Sumayya Abdul Sattar R, Verma R, Mahajan B, Singh Saluja S. Molecular markers in cancer. Clin Chim Acta 2022; 532:95-114. [DOI: https:/doi.org/10.1016/j.cca.2022.05.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
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Fernandes M, Marques H, Teixeira AL, Medeiros R. Circulating lncRNA- and miRNA-Associated ceRNA Network as a Potential Prognostic Biomarker for Non-Hodgkin Lymphoma: A Bioinformatics Analysis and a Pilot Study. Biomedicines 2022; 10:biomedicines10061322. [PMID: 35740344 PMCID: PMC9219780 DOI: 10.3390/biomedicines10061322] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 05/17/2022] [Accepted: 05/31/2022] [Indexed: 02/06/2023] Open
Abstract
Non-Hodgkin lymphoma (NHL) is characterized by a great variability in patient outcomes, resulting in the critical need for identifying new molecular prognostic biomarkers. This study aimed to identify novel circulating prognostic biomarkers based on an miRNA/lncRNA-associated ceRNA network for NHL. Using bioinformatic analysis, we identified the miRNA-lncRNA pairs, and using RT-qPCR, we analyzed their plasma levels in a cohort of 113 NHL patients to assess their prognostic value. Bioinformatic analysis identified SNHG16 and SNHG6 as hsa-miR-20a-5p and hsa-miR-181a-5p sponges, respectively. Plasma levels of hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNG6 were significantly associated with more aggressive disease and IPI/FLIPI scores. Moreover, we found that patients with risk expression profiles of hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNHG6 presented a higher risk of positive bone marrow involvement. Moreover, hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNHG6 pairs’ plasma levels were associated with overall survival and progression-free survival of NHL patients, being independent prognostic factors in a multivariate Cox analysis. The prediction models incorporating the ceRNA network expression analysis improved the predictive capacity compared to the model, which only considered the clinicopathological variables. There are still few studies on using the ceRNA network as a potential prognostic biomarker, particularly in NHL, which may permit the implementation of a more personalized management of these patients.
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Affiliation(s)
- Mara Fernandes
- 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; (M.F.); (A.L.T.)
- Research Department of the Portuguese League against Cancer Regional Nucleus of the North (LPCC-NRN), 4200-177 Porto, Portugal
- Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal
| | - Herlander Marques
- Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal;
- ICVS/3B’s—PT Government Associate Laboratory, 4805-017 Braga/Guimarães, Portugal
- Department of Oncology, Hospital de Braga, 4710-069 Braga, Portugal
- CINTESIS, Center for Health Technology and Services Research, Faculty of Medicine, University of Porto, 4200-450 Porto, Portugal
| | - Ana Luísa Teixeira
- 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; (M.F.); (A.L.T.)
- ICBAS–Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-513 Porto, 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; (M.F.); (A.L.T.)
- Research Department of the Portuguese League against Cancer Regional Nucleus of the North (LPCC-NRN), 4200-177 Porto, Portugal
- Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal
- ICBAS–Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-513 Porto, Portugal
- Biomedical Research Center (CEBIMED), Faculty of Health Sciences of Fernando Pessoa University (UFP), 4249-004 Porto, Portugal
- Correspondence: ; Tel.: +351-225084000 (ext. 5414)
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Ahmad E, Ali A, Nimisha, Kumar Sharma A, Apurva, Kumar A, Mehdi G, Sumayya Abdul Sattar R, Verma R, Mahajan B, Singh Saluja S. Molecular markers in cancer. Clin Chim Acta 2022; 532:95-114. [DOI: 10.1016/j.cca.2022.05.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 05/31/2022] [Accepted: 05/31/2022] [Indexed: 12/01/2022]
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34
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Balana C, Castañer S, Carrato C, Moran T, Lopez-Paradís A, Domenech M, Hernandez A, Puig J. Preoperative Diagnosis and Molecular Characterization of Gliomas With Liquid Biopsy and Radiogenomics. Front Neurol 2022; 13:865171. [PMID: 35693015 PMCID: PMC9177999 DOI: 10.3389/fneur.2022.865171] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 05/05/2022] [Indexed: 12/13/2022] Open
Abstract
Gliomas are a heterogenous group of central nervous system tumors with different outcomes and different therapeutic needs. Glioblastoma, the most common subtype in adults, has a very poor prognosis and disabling consequences. The World Health Organization (WHO) classification specifies that the typing and grading of gliomas should include molecular markers. The molecular characterization of gliomas has implications for prognosis, treatment planning, and prediction of treatment response. At present, gliomas are diagnosed via tumor resection or biopsy, which are always invasive and frequently risky methods. In recent years, however, substantial advances have been made in developing different methods for the molecular characterization of tumors through the analysis of products shed in body fluids. Known as liquid biopsies, these analyses can potentially provide diagnostic and prognostic information, guidance on choice of treatment, and real-time information on tumor status. In addition, magnetic resonance imaging (MRI) is another good source of tumor data; radiomics and radiogenomics can link the imaging phenotypes to gene expression patterns and provide insights to tumor biology and underlying molecular signatures. Machine and deep learning and computational techniques can also use quantitative imaging features to non-invasively detect genetic mutations. The key molecular information obtained with liquid biopsies and radiogenomics can be useful not only in the diagnosis of gliomas but can also help predict response to specific treatments and provide guidelines for personalized medicine. In this article, we review the available data on the molecular characterization of gliomas using the non-invasive methods of liquid biopsy and MRI and suggest that these tools could be used in the future for the preoperative diagnosis of gliomas.
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Affiliation(s)
- Carmen Balana
- Medical Oncology Service, Institut Català d'Oncologia Badalona (ICO), Badalona Applied Research Group in Oncology (B-ARGO Group), Institut Investigació Germans Trias i Pujol (IGTP), Barcelona, Spain
- *Correspondence: Carmen Balana
| | - Sara Castañer
- Diagnostic Imaging Institute (IDI), Hospital Universitari Germans Trias I Pujol, Institut Investigació Germans Trias i Pujol (IGTP), Barcelona, Spain
| | - Cristina Carrato
- Department of Pathology, Hospital Universitari Germans Trias I Pujol, Institut Investigació Germans Trias i Pujol (IGTP), Barcelona, Spain
| | - Teresa Moran
- Medical Oncology Service, Institut Català d'Oncologia Badalona (ICO), Badalona Applied Research Group in Oncology (B-ARGO Group), Institut Investigació Germans Trias i Pujol (IGTP), Barcelona, Spain
| | - Assumpció Lopez-Paradís
- Medical Oncology Service, Institut Català d'Oncologia Badalona (ICO), Badalona Applied Research Group in Oncology (B-ARGO Group), Institut Investigació Germans Trias i Pujol (IGTP), Barcelona, Spain
| | - Marta Domenech
- Medical Oncology Service, Institut Català d'Oncologia Badalona (ICO), Badalona Applied Research Group in Oncology (B-ARGO Group), Institut Investigació Germans Trias i Pujol (IGTP), Barcelona, Spain
| | - Ainhoa Hernandez
- Medical Oncology Service, Institut Català d'Oncologia Badalona (ICO), Badalona Applied Research Group in Oncology (B-ARGO Group), Institut Investigació Germans Trias i Pujol (IGTP), Barcelona, Spain
| | - Josep Puig
- Department of Radiology IDI [Girona Biomedical Research Institute] IDIBGI, Hospital Universitari Dr Josep Trueta, Girona, Spain
- Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain
- Comparative Medicine and Bioimage of Catalonia, Institut Investigació Germans Trias i Pujol (IGTP), Barcelona, Spain
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35
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Wilson C, Dias NW, Pancini S, Mercadante V, Biase FH. Delayed processing of blood samples impairs the accuracy of mRNA-based biomarkers. Sci Rep 2022; 12:8196. [PMID: 35581252 PMCID: PMC9113984 DOI: 10.1038/s41598-022-12178-5] [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: 01/28/2022] [Accepted: 05/03/2022] [Indexed: 11/29/2022] Open
Abstract
The transcriptome of peripheral white blood cells (PWBCs) are indicators of an organism's physiological state, thus making them a prime biological sample for mRNA-based biomarker discovery. Here, we designed an experiment to evaluate the impact of delayed processing of whole blood samples on gene transcript abundance in PWBCs. We hypothesized that storing blood samples for 24 h at 4 °C would cause RNA degradation resulting in altered transcriptome profiles. There were no statistical differences in RNA quality parameters among samples processed after one, three, six, or eight hours post collection. Additionally, no significant differences were noted in RNA quality parameters or gene transcript abundance between samples collected from the jugular and coccygeal veins. However, samples processed after 24 h of storage had a lower RNA integrity number value (P = 0.03) in comparison to those processed after one hour of storage. Using RNA-sequencing, we identified four and 515 genes with differential transcript abundance in samples processed after storage for eight and 24 h, respectively, relative to samples processed after one hour. Sequencing coverage of transcripts was similar between samples from the 24-h and one-hour groups, thus showing no indication of RNA degradation. This alteration in transcriptome profiles can impair the accuracy of mRNA-based biomarkers, therefore, blood samples collected for mRNA-based biomarker discovery should be refrigerated immediately and processed within six hours post-sampling.
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Affiliation(s)
- Chace Wilson
- School of Animal Sciences, Virginia Polytechnic Institute and State University, 175 W Campus Dr., Blacksburg, VA, 24061, USA
| | - Nicholas W Dias
- School of Animal Sciences, Virginia Polytechnic Institute and State University, 175 W Campus Dr., Blacksburg, VA, 24061, USA
| | - Stefania Pancini
- School of Animal Sciences, Virginia Polytechnic Institute and State University, 175 W Campus Dr., Blacksburg, VA, 24061, USA
| | - Vitor Mercadante
- School of Animal Sciences, Virginia Polytechnic Institute and State University, 175 W Campus Dr., Blacksburg, VA, 24061, USA
| | - Fernando H Biase
- School of Animal Sciences, Virginia Polytechnic Institute and State University, 175 W Campus Dr., Blacksburg, VA, 24061, USA.
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Drandi D, Decruyenaere P, Ferrante M, Offner F, Vandesompele J, Ferrero S. Nucleic Acid Biomarkers in Waldenström Macroglobulinemia and IgM-MGUS: Current Insights and Clinical Relevance. Diagnostics (Basel) 2022; 12:diagnostics12040969. [PMID: 35454017 PMCID: PMC9028641 DOI: 10.3390/diagnostics12040969] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 04/07/2022] [Accepted: 04/09/2022] [Indexed: 12/13/2022] Open
Abstract
Waldenström Macroglobulinemia (WM) is an indolent lymphoplasmacytic lymphoma, characterized by the production of excess immunoglobulin M monoclonal protein. WM belongs to the spectrum of IgM gammopathies, ranging from asymptomatic IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), through IgM-related disorders and asymptomatic WM to symptomatic WM. In recent years, its complex genomic and transcriptomic landscape has been extensively explored, hereby elucidating the biological mechanisms underlying disease onset, progression and therapy response. An increasing number of mutations, cytogenetic abnormalities, and molecular signatures have been described that have diagnostic, phenotype defining or prognostic implications. Moreover, cell-free nucleic acid biomarkers are increasingly being investigated, benefiting the patient in a minimally invasive way. This review aims to provide an extensive overview of molecular biomarkers in WM and IgM-MGUS, considering current shortcomings, as well as potential future applications in a precision medicine approach.
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Affiliation(s)
- Daniela Drandi
- Department of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10126 Torino, Italy; (M.F.); (S.F.)
- Correspondence: (D.D.); (P.D.)
| | - Philippe Decruyenaere
- Department of Hematology, Ghent University Hospital, 9000 Ghent, Belgium;
- OncoRNALab, Cancer Research Institute Ghent (CRIG), 9000 Ghent, Belgium;
- Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium
- Correspondence: (D.D.); (P.D.)
| | - Martina Ferrante
- Department of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10126 Torino, Italy; (M.F.); (S.F.)
| | - Fritz Offner
- Department of Hematology, Ghent University Hospital, 9000 Ghent, Belgium;
| | - Jo Vandesompele
- OncoRNALab, Cancer Research Institute Ghent (CRIG), 9000 Ghent, Belgium;
- Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium
| | - Simone Ferrero
- Department of Molecular Biotechnology and Health Sciences, Hematology Division, University of Torino, 10126 Torino, Italy; (M.F.); (S.F.)
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Allegra A, Cicero N, Tonacci A, Musolino C, Gangemi S. Circular RNA as a Novel Biomarker for Diagnosis and Prognosis and Potential Therapeutic Targets in Multiple Myeloma. Cancers (Basel) 2022; 14:cancers14071700. [PMID: 35406472 PMCID: PMC8997050 DOI: 10.3390/cancers14071700] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 03/24/2022] [Accepted: 03/25/2022] [Indexed: 01/27/2023] Open
Abstract
Circular RNAs (circRNAs) are a novel type of covalently closed RNAs involved in several physiological and pathological processes. They display tissue-specific expression and are constant, abundant, and highly conserved, making them perfect markers for diagnosis and prognosis. Several studies have proposed that circRNAs are also differentially produced in malignancies where they have oncogenic effects. Furthermore, circRNAs affecting microRNAs modify the expression profile of several transcription factors which play essential roles in tumors. CircRNAs within the hematopoietic compartment were identified as modulators of mechanisms able to enhance or suppress tumor progression in blood malignancies. Moreover, several circRNAs were suggested to confer resistance to the conventional drugs employed in hematopoietic cancers. In this review, we highlight the growing role and the controlling mechanisms by which circRNAs modify multiple myeloma genesis. We propose that circRNAs can be considered as potential diagnostic and prognostic markers, can induce chemoresistance, and might represent novel therapeutic targets for multiple myeloma.
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Affiliation(s)
- Alessandro Allegra
- Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, Division of Hematology, University of Messina, 98125 Messina, Italy;
- Correspondence:
| | - Nicola Cicero
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy;
| | - Alessandro Tonacci
- Clinical Physiology Institute, National Research Council of Italy (IFC-CNR), 56124 Pisa, Italy;
| | - Caterina Musolino
- Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, Division of Hematology, University of Messina, 98125 Messina, Italy;
| | - Sebastiano Gangemi
- Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy;
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Comprehensive RNA dataset of tissue and plasma from patients with esophageal cancer or precursor lesions. Sci Data 2022; 9:86. [PMID: 35288573 PMCID: PMC8921197 DOI: 10.1038/s41597-022-01176-x] [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: 03/30/2021] [Accepted: 01/25/2022] [Indexed: 11/29/2022] Open
Abstract
AbstractIn the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett’s esophagus. Per patient, a blood plasma sample, and a healthy and disease esophageal tissue sample were included. In total, this comprehensive dataset consists of 102 sequenced libraries from 51 samples. Based on this data, 119 expression profiles are available for three biotypes, including miRNA (51), mRNA (51) and circRNA (17). This unique resource allows for discovery of novel biomarkers and disease mechanisms, comparison of tissue and liquid biopsy profiles, integration of coding and non-coding RNA patterns, and can serve as a validation dataset in other RNA landscaping studies. Moreover, structural RNA differences can be identified in this dataset, including protein coding mutations, fusion genes, and circular RNAs.
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Melixetian M, Pelicci PG, Lanfrancone L. Regulation of LncRNAs in Melanoma and Their Functional Roles in the Metastatic Process. Cells 2022; 11:577. [PMID: 35159386 PMCID: PMC8834033 DOI: 10.3390/cells11030577] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/02/2022] [Accepted: 02/05/2022] [Indexed: 02/06/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) are key regulators of numerous intracellular processes leading to tumorigenesis. They are frequently deregulated in cancer, functioning as oncogenes or tumor suppressors. As they act through multiple mechanisms, it is not surprising that they may exert dual functions in the same tumor. In melanoma, a highly invasive and metastatic tumor with the propensity to rapidly develop drug resistance, lncRNAs play different roles in: (i) guiding the phenotype switch and leading to metastasis formation; (ii) predicting the response of melanoma patients to immunotherapy; (iii) triggering adaptive responses to therapy and acquisition of drug resistance phenotypes. In this review we summarize the most recent findings on the lncRNAs involved in melanoma growth and spreading to distant sites, focusing on their role as biomarkers for disease diagnosis and patient prognosis, or targets for novel therapeutic approaches.
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Affiliation(s)
- Marine Melixetian
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy; (M.M.); (P.G.P.)
| | - Pier Giuseppe Pelicci
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy; (M.M.); (P.G.P.)
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy
| | - Luisa Lanfrancone
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy; (M.M.); (P.G.P.)
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Roalsø MTT, Hald ØH, Alexeeva M, Søreide K. Emerging Role of Epigenetic Alterations as Biomarkers and Novel Targets for Treatments in Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2022; 14:cancers14030546. [PMID: 35158814 PMCID: PMC8833770 DOI: 10.3390/cancers14030546] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/05/2022] [Accepted: 01/17/2022] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Epigenetic alterations cause changes in gene expression without affecting the DNA sequence and are found to affect several molecular pathways in pancreatic tumors. Such changes are reversible, making them potential drug targets. Furthermore, epigenetic alterations occur early in the disease course and may thus be explored for early detection. Hence, a deeper understanding of epigenetics in pancreatic cancer may lead to improved diagnostics, treatments, and prognostication. Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited treatment options. Emerging evidence shows that epigenetic alterations are present in PDAC. The changes are potentially reversible and therefore promising therapeutic targets. Epigenetic aberrations also influence the tumor microenvironment with the potential to modulate and possibly enhance immune-based treatments. Epigenetic marks can also serve as diagnostic screening tools, as epigenetic changes occur at early stages of the disease. Further, epigenetics can be used in prognostication. The field is evolving, and this review seeks to provide an updated overview of the emerging role of epigenetics in the diagnosis, treatment, and prognostication of PDAC.
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Affiliation(s)
- Marcus T. T. Roalsø
- Department of Quality and Health Technology, University of Stavanger, 4036 Stavanger, Norway;
- HPB Unit, Department of Gastrointestinal Surgery, Stavanger University Hospital, 4068 Stavanger, Norway;
- Gastrointestinal Translational Research Unit, Laboratory for Molecular Medicine, Stavanger University Hospital, 4068 Stavanger, Norway
| | - Øyvind H. Hald
- Department of Oncology, University Hospital of North Norway, 9038 Tromsø, Norway;
| | - Marina Alexeeva
- HPB Unit, Department of Gastrointestinal Surgery, Stavanger University Hospital, 4068 Stavanger, Norway;
- Gastrointestinal Translational Research Unit, Laboratory for Molecular Medicine, Stavanger University Hospital, 4068 Stavanger, Norway
| | - Kjetil Søreide
- HPB Unit, Department of Gastrointestinal Surgery, Stavanger University Hospital, 4068 Stavanger, Norway;
- Gastrointestinal Translational Research Unit, Laboratory for Molecular Medicine, Stavanger University Hospital, 4068 Stavanger, Norway
- Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
- Correspondence:
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41
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Li B, Ren Q, Li Y, Tian S, Chong Y, Sun S, Feng F. Screening differential circular RNA expression profiles reveals the regulatory role of circMARS in anti-tuberculosis drug-induced liver injury. J Cell Mol Med 2022; 26:1050-1059. [PMID: 35032098 PMCID: PMC8831982 DOI: 10.1111/jcmm.17157] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 07/13/2021] [Accepted: 12/17/2021] [Indexed: 01/09/2023] Open
Abstract
Tuberculosis (TB) treatment is plagued by liver damage, which often leads to treatment interruptions. Circular RNAs (circRNAs) are a special class of non‐coding RNAs abundant in body fluids with important biological functions. However, the role of circRNA in anti‐tuberculosis drug‐induced liver injury (ADLI) is unclear. We explored ADLI‐specific circRNAs in TB patients using circRNA microarrays and verified circMARS in a cohort of 300 individuals. In addition to the value assessment of circMARS in patients using a receiver operating characteristic (ROC) curve, cell experiments were also performed under the guidance of bioinformatics analyses. In particular, we found that circMARS acts as a miRNA sponge by binding to miRNAs. Compared with the blank group, the expressions of circMARS, KMT2C gene, and EGFR protein in the ADLI group were increased, while miR‐6808‐5p, miR‐6874‐3p, and miR‐3157‐5p were decreased. Furthermore, when si‐circMARS was used in the ADLI groups, circMARS demotion manifested the opposite results. Subsequently, a self‐controlled cohort of 35 participants was used to verify the circMARS–miR‐6808‐5p/‐6874‐3p/‐3157‐5p–KMT2C–EGFR function axis. Therefore, circMARS may participate in the compensatory repair mechanism of ADLI through the function axis, and may be a potential biomarker for ADLI diagnosis in TB patients.
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Affiliation(s)
- Biao Li
- School of Public Health, North China University of Science and Technology, Tangshan, China.,Xiaoshan District Center for Disease Control and Prevention, Hangzhou, China
| | - Qi Ren
- School of Public Health, North China University of Science and Technology, Tangshan, China
| | - Yuhong Li
- School of Public Health, North China University of Science and Technology, Tangshan, China
| | - Shenqian Tian
- School of Public Health, North China University of Science and Technology, Tangshan, China
| | - Yingzhi Chong
- School of Public Health, North China University of Science and Technology, Tangshan, China
| | - Shufeng Sun
- College of Nursing and Rehabilitation, North China University of Science and Technology, Tangshan, China
| | - Fumin Feng
- School of Public Health, North China University of Science and Technology, Tangshan, China.,School of Life Science, North China University of Science and Technology, Tangshan, China
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42
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Novel Diagnostic Biomarkers in Colorectal Cancer. Int J Mol Sci 2022; 23:ijms23020852. [PMID: 35055034 PMCID: PMC8776048 DOI: 10.3390/ijms23020852] [Citation(s) in RCA: 125] [Impact Index Per Article: 41.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 12/27/2021] [Accepted: 01/03/2022] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is still a leading cause of cancer death worldwide. Less than half of cases are diagnosed when the cancer is locally advanced. CRC is a heterogenous disease associated with a number of genetic or somatic mutations. Diagnostic markers are used for risk stratification and early detection, which might prolong overall survival. Nowadays, the widespread use of semi-invasive endoscopic methods and feacal blood tests characterised by suboptimal accuracy of diagnostic results has led to the detection of cases at later stages. New molecular noninvasive tests based on the detection of CRC alterations seem to be more sensitive and specific then the current methods. Therefore, research aiming at identifying molecular markers, such as DNA, RNA and proteins, would improve survival rates and contribute to the development of personalized medicine. The identification of “ideal” diagnostic biomarkers, having high sensitivity and specificity, being safe, cheap and easy to measure, remains a challenge. The purpose of this review is to discuss recent advances in novel diagnostic biomarkers for tumor tissue, blood and stool samples in CRC patients.
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Circulating MicroRNAs as Cancer Biomarkers in Liquid Biopsies. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1385:23-73. [DOI: 10.1007/978-3-031-08356-3_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Fernandes M, Marques H, Teixeira AL, Medeiros R. ceRNA Network of lncRNA/miRNA as Circulating Prognostic Biomarkers in Non-Hodgkin Lymphomas: Bioinformatic Analysis and Assessment of Their Prognostic Value in an NHL Cohort. Int J Mol Sci 2021; 23:ijms23010201. [PMID: 35008626 PMCID: PMC8745130 DOI: 10.3390/ijms23010201] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 12/20/2021] [Accepted: 12/22/2021] [Indexed: 12/24/2022] Open
Abstract
Research has been focusing on identifying novel biomarkers to better stratify non-Hodgkin lymphoma patients based on prognosis. Studies have demonstrated that lncRNAs act as miRNA sponges, creating ceRNA networks to regulate mRNA expression, and its deregulation is associated with lymphoma development. This study aimed to identify novel circulating prognostic biomarkers based on miRNA/lncRNA-associated ceRNA network for NHL. Herein, bioinformatic analysis was performed to construct ceRNA networks for hsa-miR-150-5p and hsa-miR335-5p. Then, the prognostic value of the miRNA–lncRNA pairs’ plasma levels was assessed in a cohort of 113 NHL patients. Bioinformatic analysis identified MALAT1 and NEAT1 as hsa-miR-150-5p and has-miR-335-5p sponges, respectively. Plasma hsa-miR-150-5p/MALAT1 and hsa-miR335-5p/NEAT1 levels were significantly associated with more aggressive and advanced disease. The overall survival and progression-free survival analysis indicated that hsa-miR-150-5p/MALAT1 and hsa-miR335-5p/NEAT1 pairs’ plasma levels were remarkably associated with NHL patients’ prognosis, being independent prognostic factors in a multivariate Cox analysis. Low levels of hsa-miR-150-5p and hsa-miR-335-5p combined with high levels of the respective lncRNA pair were associated with poor prognosis of NHL patients. Overall, the analysis of ceRNA network expression levels may be a useful prognostic biomarker for NHL patients and could identify patients who could benefit from more intensive treatments.
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MESH Headings
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Cohort Studies
- Computational Biology
- Disease-Free Survival
- Gene Expression Regulation, Neoplastic
- Gene Regulatory Networks
- Humans
- Lymphoma, Non-Hodgkin/blood
- Lymphoma, Non-Hodgkin/genetics
- MicroRNAs/blood
- MicroRNAs/genetics
- MicroRNAs/metabolism
- Prognosis
- RNA, Long Noncoding/blood
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Risk Factors
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Affiliation(s)
- Mara Fernandes
- 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; (M.F.); (A.L.T.)
- Research Department of the Portuguese League against Cancer Regional Nucleus of the North (LPCC-NRN), 4200-177 Porto, Portugal
- Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal
| | - Herlander Marques
- Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal;
- ICVS/3B’s—PT Government Associate Laboratory, 4805-017 Braga/Guimarães, Portugal
- Department of Oncology, Hospital de Braga, 4710-243 Braga, Portugal
- CINTESIS, Center for Health Technology and Services Research, Faculty of Medicine, University of Porto, 4200-450 Porto, Portugal
| | - Ana Luísa Teixeira
- 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; (M.F.); (A.L.T.)
- ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-513 Porto, 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; (M.F.); (A.L.T.)
- Research Department of the Portuguese League against Cancer Regional Nucleus of the North (LPCC-NRN), 4200-177 Porto, Portugal
- Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal
- ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-513 Porto, Portugal
- Biomedical Research Center (CEBIMED), Faculty of Health Sciences of Fernando Pessoa University (UFP), 4249-004 Porto, Portugal
- Correspondence: ; Tel.: +351-225-084-000 (ext. 5414)
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Jiang T, Wang H, Liu L, Song H, Zhang Y, Wang J, Liu L, Xu T, Fan R, Xu Y, Wang S, Shi L, Zheng L, Wang R, Song J. CircIL4R activates the PI3K/AKT signaling pathway via the miR-761/TRIM29/PHLPP1 axis and promotes proliferation and metastasis in colorectal cancer. Mol Cancer 2021; 20:167. [PMID: 34922544 PMCID: PMC8684286 DOI: 10.1186/s12943-021-01474-9] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 12/01/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Accumulating studies have revealed that aberrant expression of circular RNAs (circRNAs) is widely involved in the tumorigenesis and progression of malignant cancers, including colorectal cancer (CRC). Nevertheless, the clinical significance, levels, features, biological function, and molecular mechanisms of novel circRNAs in CRC remain largely unexplored. METHODS CRC-related circRNAs were identified through bioinformatics analysis and verified in clinical specimens by qRT-PCR and in situ hybridization (ISH). Then, in vitro and in vivo experiments were performed to determine the clinical significance of, functional roles of, and clinical characteristics associated with circIL4R in CRC specimens and cells. Mechanistically, RNA pull-down, fluorescence in situ hybridization (FISH), luciferase reporter, and ubiquitination assays were performed to confirm the underlying mechanism of circIL4R. RESULTS CircIL4R was upregulated in CRC cell lines and in sera and tissues from CRC patients and was positively correlated with advanced clinicopathological features and poor prognosis. Functional experiments demonstrated that circIL4R promotes CRC cell proliferation, migration, and invasion via the PI3K/AKT signaling pathway. Mechanistically, circIL4R was regulated by TFAP2C and competitively interacted with miR-761 to enhance the expression of TRIM29, thereby targeting PHLPP1 for ubiquitin-mediated degradation to activate the PI3K/AKT signaling pathway and consequently facilitate CRC progression. CONCLUSIONS Our findings demonstrate that upregulation of circIL4R plays an oncogenic role in CRC progression and may serve as a promising diagnostic and prognostic biomarker for CRC detection and as a potential therapeutic target for CRC treatment.
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Affiliation(s)
- Tao Jiang
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China
| | - Hongyu Wang
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.,The Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Lianyu Liu
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.,The Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Hu Song
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China
| | - Yi Zhang
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China
| | - Jiaqi Wang
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China
| | - Lei Liu
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.,The Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Teng Xu
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China
| | - Ruizhi Fan
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China
| | - Yixin Xu
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China
| | - Shuai Wang
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.,The Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Linsen Shi
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China
| | - Li Zheng
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing, China
| | - Renhao Wang
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China. .,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China.
| | - Jun Song
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China. .,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China.
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Wen G, Zhou T, Gu W. The potential of using blood circular RNA as liquid biopsy biomarker for human diseases. Protein Cell 2021; 12:911-946. [PMID: 33131025 PMCID: PMC8674396 DOI: 10.1007/s13238-020-00799-3] [Citation(s) in RCA: 110] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 10/09/2020] [Indexed: 12/14/2022] Open
Abstract
Circular RNA (circRNA) is a novel class of single-stranded RNAs with a closed loop structure. The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing. Their expression is dynamically regulated and shows spatiotemporal patterns among cell types, tissues and developmental stages. CircRNAs have important biological functions in many physiological processes, and their aberrant expression is implicated in many human diseases. Due to their high stability, circRNAs are becoming promising biomarkers in many human diseases, such as cardiovascular diseases, autoimmune diseases and human cancers. In this review, we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases. We highlight their abundant expression, essential biological functions and significant correlations to human diseases in various components of peripheral blood, including whole blood, blood cells and extracellular vesicles. In addition, we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.
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Affiliation(s)
- Guoxia Wen
- State Key Laboratory of Bioelectronics, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Tong Zhou
- Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, 89557, USA.
| | - Wanjun Gu
- State Key Laboratory of Bioelectronics, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, 210096, China.
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47
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Zhang Y, Wang Y, Su X, Wang P, Lin W. The Value of Circulating Circular RNA in Cancer Diagnosis, Monitoring, Prognosis, and Guiding Treatment. Front Oncol 2021; 11:736546. [PMID: 34722285 PMCID: PMC8551378 DOI: 10.3389/fonc.2021.736546] [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: 07/05/2021] [Accepted: 09/23/2021] [Indexed: 12/31/2022] Open
Abstract
Liquid biopsy includes non-invasive analysis of circulating tumor-derived substances. It is a novel, innovative cancer screening tool that overcomes the limitations of current invasive tissue examinations in precision oncology. Circular RNA (circRNA) is a recent, novel, and attractive liquid biomarker showing stability, abundance, and high specificity in various diseases, especially in human cancers. This review focused on the emerging potential of human circRNA in body fluids as the liquid biopsy biomarkers for cancers and the methods used to detect the circRNA expression and summarized the construction of circRNA biomarkers in body fluids for treating human cancers and their limitations before they become part of routine clinical medicine. Furthermore, the future opportunities and challenges of translating circRNAs in liquid biopsy into clinical practices were explored.
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Affiliation(s)
- Yunjing Zhang
- Department of Nephrology, The Fourth Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Jinhua, China
| | - Ying Wang
- Department of Nephrology, The Fourth Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Jinhua, China
| | - Xinwan Su
- Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ping Wang
- Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Weiqiang Lin
- Department of Nephrology, The Fourth Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Jinhua, China
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Greco F, Anastasi F, Pardini LF, Dilillo M, Vannini E, Baroncelli L, Caleo M, McDonnell LA. Longitudinal Bottom-Up Proteomics of Serum, Serum Extracellular Vesicles, and Cerebrospinal Fluid Reveals Candidate Biomarkers for Early Detection of Glioblastoma in a Murine Model. Molecules 2021; 26:5992. [PMID: 34641541 PMCID: PMC8512455 DOI: 10.3390/molecules26195992] [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: 08/31/2021] [Revised: 09/24/2021] [Accepted: 09/30/2021] [Indexed: 12/04/2022] Open
Abstract
Glioblastoma Multiforme (GBM) is a brain tumor with a poor prognosis and low survival rates. GBM is diagnosed at an advanced stage, so little information is available on the early stage of the disease and few improvements have been made for earlier diagnosis. Longitudinal murine models are a promising platform for biomarker discovery as they allow access to the early stages of the disease. Nevertheless, their use in proteomics has been limited owing to the low sample amount that can be collected at each longitudinal time point. Here we used optimized microproteomics workflows to investigate longitudinal changes in the protein profile of serum, serum small extracellular vesicles (sEVs), and cerebrospinal fluid (CSF) in a GBM murine model. Baseline, pre-symptomatic, and symptomatic tumor stages were determined using non-invasive motor tests. Forty-four proteins displayed significant differences in signal intensities during GBM progression. Dysregulated proteins are involved in cell motility, cell growth, and angiogenesis. Most of the dysregulated proteins already exhibited a difference from baseline at the pre-symptomatic stage of the disease, suggesting that early effects of GBM might be detectable before symptom onset.
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Affiliation(s)
- Francesco Greco
- Institute of Life Sciences, Sant’Anna School of Advanced Studies, 56127 Pisa, Italy;
- Fondazione Pisana per la Scienza ONLUS, 56017 San Giuliano Terme, Italy; (F.A.); (L.F.P.); (M.D.)
| | - Federica Anastasi
- Fondazione Pisana per la Scienza ONLUS, 56017 San Giuliano Terme, Italy; (F.A.); (L.F.P.); (M.D.)
- NEST Laboratories, Scuola Normale Superiore, 56127 Pisa, Italy
| | - Luca Fidia Pardini
- Fondazione Pisana per la Scienza ONLUS, 56017 San Giuliano Terme, Italy; (F.A.); (L.F.P.); (M.D.)
- Department of Chemistry and Industrial Chemistry, University of Pisa, 56124 Pisa, Italy
| | - Marialaura Dilillo
- Fondazione Pisana per la Scienza ONLUS, 56017 San Giuliano Terme, Italy; (F.A.); (L.F.P.); (M.D.)
| | - Eleonora Vannini
- CNR, Neuroscience Institute, 56124 Pisa, Italy; (E.V.); (L.B.); (M.C.)
- Fondazione Umberto Veronesi, 20122 Milano, Italy
| | - Laura Baroncelli
- CNR, Neuroscience Institute, 56124 Pisa, Italy; (E.V.); (L.B.); (M.C.)
- IRCCS Fondazione Stella Maris, 56018 Calambrone, Italy
| | - Matteo Caleo
- CNR, Neuroscience Institute, 56124 Pisa, Italy; (E.V.); (L.B.); (M.C.)
- Dipartimento di Scienze Biomediche, Università di Padova, 35131 Padova, Italy
| | - Liam A. McDonnell
- Fondazione Pisana per la Scienza ONLUS, 56017 San Giuliano Terme, Italy; (F.A.); (L.F.P.); (M.D.)
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Chivu-Economescu M, Necula L, Matei L, Dragu D, Bleotu C, Diaconu CC. Clinical Applications of Liquid Biopsy in Gastric Cancer. Front Med (Lausanne) 2021; 8:749250. [PMID: 34651002 PMCID: PMC8505538 DOI: 10.3389/fmed.2021.749250] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 08/31/2021] [Indexed: 02/05/2023] Open
Abstract
Liquid biopsy represents an exciting new area in the field of cancer diagnosis and management, offering a less invasive and more convenient approach to obtain a time-point image of the tumor burden and its genomic profile. Samples collected from several body fluids, mostly blood, can be used to gain access to circulating tumor cells and DNA, non-coding RNAs, microRNAs, and exosomes, at any moment, offering a dynamic picture of the tumor. For patients with GC, the use of blood-based biopsies may be particularly beneficial since tissue biopsies are difficult to obtain and cause real distress to the patient. With advantages such as repeatability and minimal invasion, it is no wonder that the field of liquid biopsy has received tremendous attention. However, the abundance of studies, involving a wide range of assays with different principles, prevented for the moment the reproducibility of the results and therefore the translation into the clinic of liquid biopsy. In this review, we present the latest technical development and data on circulating biomarkers available through liquid biopsy in gastric cancer with an emphasis on their clinical utility in areas such as cancer screening, prognostic stratification, and therapeutic management.
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Affiliation(s)
- Mihaela Chivu-Economescu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest, Romania
| | - Laura Necula
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest, Romania
- Faculty of Medicine, Titu Maiorescu University, Bucharest, Romania
| | - Lilia Matei
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest, Romania
| | - Denisa Dragu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest, Romania
| | - Coralia Bleotu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest, Romania
| | - Carmen C. Diaconu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest, Romania
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50
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Epigenetic Biomarkers of Renal Cell Carcinoma for Liquid Biopsy Tests. Int J Mol Sci 2021; 22:ijms22168846. [PMID: 34445557 PMCID: PMC8396354 DOI: 10.3390/ijms22168846] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 08/06/2021] [Accepted: 08/13/2021] [Indexed: 12/16/2022] Open
Abstract
Renal cell carcinomas (RCC) account for 2–3% of the global cancer burden and are characterized by the highest mortality rate among all genitourinary cancers. However, excluding conventional imagining approaches, there are no reliable diagnostic and prognostic tools available for clinical use at present. Liquid biopsies, such as urine, serum, and plasma, contain a significant amount of tumor-derived nucleic acids, which may serve as non-invasive biomarkers that are particularly useful for early cancer detection, follow-up, and personalization of treatment. Changes in epigenetic phenomena, such as DNA methylation level, expression of microRNAs (miRNAs), and long noncoding RNAs (lncRNAs), are observed early during cancer development and are easily detectable in biofluids when morphological changes are still undetermined by conventional diagnostic tools. Here, we reviewed recent advances made in the development of liquid biopsy-derived DNA methylation-, miRNAs- and lncRNAs-based biomarkers for RCC, with an emphasis on the performance characteristics. In the last two decades, a mass of circulating epigenetic biomarkers of RCC were suggested, however, most of the studies done thus far analyzed biomarkers selected from the literature, used relatively miniature, local, and heterogeneous cohorts, and suffered from a lack of sufficient validations. In summary, for improved translation into the clinical setting, there is considerable demand for the validation of the existing pool of RCC biomarkers and the discovery of novel ones with better performance and clinical utility.
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