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1
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Juthani R, Manne A. Blood-based biomarkers in pancreatic ductal adenocarcinoma: developments over the last decade and what holds for the future- a review. Front Oncol 2025; 15:1555963. [PMID: 40330826 PMCID: PMC12052548 DOI: 10.3389/fonc.2025.1555963] [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: 01/06/2025] [Accepted: 03/24/2025] [Indexed: 05/08/2025] Open
Abstract
Pancreatic Ductal Adenocarcinoma (PDAC) accounts for a significant burden of global cancer deaths worldwide. The dismal outcomes associated with PDAC can be overcome by detecting the disease early and developing tools that predict response to treatment, allowing the selection of the most optimal treatment. Over the last couple of years, significant progress has been made in the development of novel biomarkers that aid in diagnosis, prognosis, treatment selection, and monitoring response. Blood-based biomarkers offer an alternative to tissue-based diagnosis and offer immense potential in managing PDAC. In this review, we have discussed the advances in blood-based biomarkers in PDAC, such as DNA (mutations and methylations), RNA, protein biomarkers and circulating tumor cells (CTC) over the last decade and also elucidated all aspects of practical implementation of these biomarkers in clinical practice. We have also discussed implementing multiomics utilizing more than one biomarker and targeted therapies that have been developed using these biomarkers.
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Affiliation(s)
- Ronit Juthani
- Department of Medicine, Saint Vincent Hospital, Worcester, MA, United States
| | - Ashish Manne
- Department of Internal Medicine, Division of Medical Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States
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2
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Wang X, Li Z, Zhang C. Integrated Analysis of Serum and Tissue microRNA Transcriptome for Biomarker Discovery in Gastric Cancer. ENVIRONMENTAL TOXICOLOGY 2025; 40:281-290. [PMID: 39400980 DOI: 10.1002/tox.24430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 05/25/2024] [Accepted: 08/31/2024] [Indexed: 10/15/2024]
Abstract
Gastric cancer (GC) poses a significant global health challenge, demanding a detailed exploration of its molecular landscape. Studies suggest that exposure to environmental pollutants can lead to changes in microRNA (miRNA) expression patterns, which may contribute to the development and progression of GC. MiRNAs have emerged as crucial regulators implicated in GC pathogenesis. The largest GC serum miRNA dataset to date, comprising 1417 non-cancer controls and 1417 GC samples was used. We conducted a comprehensive analysis of miRNA expression profiles. Differential expression analysis, co-expression network construction, and machine learning models were employed to identify key serum miRNAs and their association with clinical parameters. Weighted Gene Co-expression Network Analysis (WGCNA) and immune infiltration analysis were used to validate the importance of the key miRNA. A total of 1766 differentially expressed miRNAs were identified, with miR-1290, miR-1246, and miR-451a among the top up-regulated, and miR-6875-5p, miR-6784-5p, miR-1228-5p, and miR-6765-5p among the top down-regulated. WGCNA revealed that modules M1 and M5 were significantly associated with GC subtypes and disease status. MiRNA-target gene network analysis identified prognostically significant genes TP53, EMCN, CBX8, and ALDH1A3. Machine learning models LASSO, SVM, randomforest, and XGBOOST demonstrated the diagnostic potential of miRNA profiles. Tissue and serum miR-187 emerged as an independent prognostic factor, influencing patient survival across clinical parameters. Gene expression and immune cell infiltration were different in tissues stratified by miR-187 expression. In summary, the integration of differential gene expression, co-expression analysis, and immune cell profiling provided insights into the molecular intricacies of GC progression.
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Affiliation(s)
- Xinfeng Wang
- Department of Pharmacy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Zhuoran Li
- Department of Optometry, Fenyang College of Shanxi Medical University, Fenyang, China
| | - Chengyan Zhang
- Department of Gastroenterology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
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3
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Corradi C, Gentiluomo M, Adsay V, Sainz J, Camisa PR, Wlodarczyk B, Crippa S, Tavano F, Capurso G, Campa D. Multi-omic markers of intraductal papillary mucinous neoplasms progression into pancreatic cancer. Semin Cancer Biol 2025; 109:25-43. [PMID: 39733817 DOI: 10.1016/j.semcancer.2024.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/19/2024] [Accepted: 12/23/2024] [Indexed: 12/31/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal and common form of pancreatic cancer, it has no specific symptoms, and most of the patients are diagnosed when the disease is already at an advanced stage. Chemotherapy typically has only a modest effect, making surgery the most effective treatment option. However, only a small percentage of patients are amenable to surgery. One viable strategy to reduce PDAC death burden associated with the disease is to focus on precursor lesions and identify markers able to predict who will evolve into PDAC. While most PDACs are believed to be preceded by pancreatic intraepithelial neoplasms (PanINs), 5-10 % arise from Intraductal papillary mucinous neoplasms (IPMNs), which are mass-forming cystic lesions that are very common in the general population. IPMNs offer an invaluable model of pancreatic carcinogenesis for researchers to analyse, as well as a target population for PDAC early detection by clinicians. The evolution of IPMN into cancer is a complex and multistep process, therefore the identification of individual markers will not be the solution. In recent years, multiple omics technologies have been instrumental to identify possible biomarkers of IPMN progression and carcinogenesis. The only foreseeable strategy will be to integrate multi-omics data, alongside clinical and morphological features, into a progression score or signature using either standard epidemiologic tools or artificial intelligence. The aim of this manuscript is to review the current knowledge on genetic biomarkers and to briefly mention also additional omics, such as metabolomics, the exposome, the miRNome and epigenomics of IPMNs.
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Affiliation(s)
| | | | - Volkan Adsay
- Department of Pathology, Koç University School of Medicine and Koç University Research Center for Translational Medicine, Istanbul, Turkey
| | - Juan Sainz
- Department of Biochemistry and Molecular Biology, University of Granada, Granada, Spain
| | - Paolo Riccardo Camisa
- Division of Pancreatic Surgery and Transplantation, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Barbara Wlodarczyk
- Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
| | - Stefano Crippa
- Division of Pancreatic Surgery and Transplantation, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Francesca Tavano
- Division of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy
| | - Gabriele Capurso
- Vita-Salute San Raffaele University, Milan, Italy; Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Daniele Campa
- Department of Biology, University of Pisa, Pisa, Italy.
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Nagarajan Y, Chandrasekaran N, Deepa Parvathi V. Functionalized Nanomaterials In Pancreatic Cancer Theranostics And Molecular Imaging. ChemistryOpen 2025; 14:e202400232. [PMID: 39434498 PMCID: PMC11726697 DOI: 10.1002/open.202400232] [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: 07/09/2024] [Revised: 08/13/2024] [Indexed: 10/23/2024] Open
Abstract
Pancreatic cancer (PC) is one of the most fatal malignancies in the world. This lethality persists due to lack of effective and efficient treatment strategies. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive epithelial malignancy which has a high incidence rate and contributes to overall cancer fatalities. As of 2022, pancreatic cancer contributes to about 3 % of all cancers globally. Over the years, research has characterised germline predisposition, the origin cell, precursor lesions, genetic alterations, structural alterations, transcriptional changes, tumour heterogeneity, metastatic progression, and the tumour microenvironment, which has improved the understanding of PDAC carcinogenesis. By using molecular-based target therapies, these fundamental advancements support primary prevention, screening, early detection, and treatment. The focus of this review is the use of targeted nanoparticles as an alternative to conventional pancreatic cancer treatment due to the various side effects of the latter. The principles of nanoparticle based cancer therapy is efficient targeting of tumour cells via enhanced permeability and retention (EPR) effects and decrease the chemotherapy side effects due to their non-specificity. To increase the efficiency of existing therapies and modify target nanoparticles, several molecular markers of pancreatic cancer cells have been identified. Thus pancreatic cancer cells can be detected using appropriately functionalized nanoparticles with specific signalling molecules. Once cancer has been identified, these nanoparticles can kill the tumour by inducing hyperthermia, medication delivery, immunotherapy or gene therapy. As potent co-delivery methods for adjuvants and tumor-associated antigens; nanoparticles (NPs) have demonstrated significant promise as delivery vehicles in cancer therapy. This ensures the precise internalization of the functionalized nanoparticle and thus also activates the immune system effectively against tumor cells. This review also discusses the immunological factors behind the uptake of functionalized nanoparticles in cancer therapies. Theranostics, which combine imaging and therapeutic chemicals in a single nanocarrier, are the next generation of medicines. Pancreatic cancer treatment may be revolutionised by the development of a tailored nanocarrier with diagnostic, therapeutic, and imaging capabilities. It is extremely difficult to incorporate various therapeutic modalities into a single nanocarrier without compromising the individual functionalities. Surface modification of nanocarriers with antibodies or proteins will enable to attain multifunctionality which increases the efficiency of pancreatic cancer therapy.
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Affiliation(s)
- Yoghalakshmi Nagarajan
- Department of Biomedical SciencesFaculty of Biomedical Sciences & TechnologySri Ramachandra Institute of Higher Education and Research (SRIHER)Tamil NaduChennai600116India
| | - Natarajan Chandrasekaran
- Senior Professor & Former DirectorCentre for NanobiotechnologyVellore Institute of Technology (VIT)Vellore Campus, Tiruvalam roadTamil NaduKatpadiVellore 632014
| | - Venkatachalam Deepa Parvathi
- Department of Biomedical SciencesFaculty of Biomedical Sciences & TechnologySri Ramachandra Institute of Higher Education and Research (SRIHER)Tamil NaduChennai600116India
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Ferreira M, Morais M, Medeiros R, Teixeira AL. MicroRNAs as Promising Therapeutic Agents Against Prostate Cancer Resistant to Castration-Where Are We Now? Pharmaceutics 2024; 16:1347. [PMID: 39598472 PMCID: PMC11597238 DOI: 10.3390/pharmaceutics16111347] [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: 09/02/2024] [Revised: 10/17/2024] [Accepted: 10/19/2024] [Indexed: 11/29/2024] Open
Abstract
MicroRNAs are a conserved class of small, tissue-specific, non-coding RNAs that regulate gene expression to preserve cellular homeostasis. Proper miRNA expression is crucial for physiological balance because it affects numerous genetic pathways, including cell cycle control, proliferation, and apoptosis, through gene expression targeting. Deregulated miRNA expression has been implicated in several cancer types, including prostate cancer (PC), acting as tumor suppressors or oncogenes. Despite the availability of promising therapies to control tumor growth and progression, effective diagnostic and therapeutic strategies for different types of cancer are still lacking. PC continues to be a significant health challenge, particularly its castration-resistant (CRPC) form, which presents major therapeutic obstacles because of its resistance to conventional androgen deprivation treatments. This review explores miRNAs' critical roles in gene regulation and cancer biology, as well as various miRNA delivery systems, highlighting their potential and the challenges in effectively targeting cancer cells. It aims to provide a comprehensive overview of the status of miRNA research in the fight against CRPC, summarizing miRNA-based therapies' successes and limitations. It also highlights the promise of miRNAs as therapeutic agents for CRPC, underlining the need for further research to overcome existing challenges and move these therapies toward clinical applications.
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Affiliation(s)
- Mariana Ferreira
- 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.); (M.M.); (R.M.)
- ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
| | - Mariana Morais
- 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.); (M.M.); (R.M.)
- ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, 4050-313 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.); (M.M.); (R.M.)
- ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
- Biomedical Research Center (CEBIMED), Faculty of Health Sciences, Fernando Pessoa University (UFP), 4249-004 Porto, Portugal
- Research Department, LPCC-Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal
- Faculty of Medicine (FMUP), University of Porto, 4200-319 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.); (M.M.); (R.M.)
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McMurry HS, Rivero JD, Chen EY, Kardosh A, Lopez CD, Pegna GJ. Gastroenteropancreatic neuroendocrine tumors: Epigenetic landscape and clinical implications. Curr Probl Cancer 2024; 52:101131. [PMID: 39173542 DOI: 10.1016/j.currproblcancer.2024.101131] [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: 02/21/2024] [Accepted: 05/22/2024] [Indexed: 08/24/2024]
Abstract
Neuroendocrine tumors (NETs) are a rare, heterogenous group of neoplasms arising from cells of the neuroendocrine system. Amongst solid tumor malignancies, NETs are notable for overall genetic stability and recent data supports the notion that epigenetic changes may drive NET pathogenesis. In this review, major epigenetic mechanisms of NET pathogenesis are reviewed, including changes in DNA methylation, histone modification, chromatin remodeling, and microRNA. Prognostic implications of the above are discussed, as well as the expanding diagnostic utility of epigenetic markers in NETs. Lastly, preclinical and clinical evaluations of epigenetically targeted therapies in NETs and are reviewed, with a focus on future directions in therapeutic advancement.
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Affiliation(s)
- Hannah S McMurry
- Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, United States
| | - Jaydira Del Rivero
- Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Emerson Y Chen
- Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, United States
| | - Adel Kardosh
- Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, United States
| | - Charles D Lopez
- Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, United States
| | - Guillaume J Pegna
- Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, United States.
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7
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Butz H, Patócs A, Igaz P. Circulating non-coding RNA biomarkers of endocrine tumours. Nat Rev Endocrinol 2024; 20:600-614. [PMID: 38886617 DOI: 10.1038/s41574-024-01005-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/23/2024] [Indexed: 06/20/2024]
Abstract
Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of malignancy, prognosis and follow-up in several neoplasms, including endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. Most of these tumours are classified as neuroendocrine neoplasms (comprised of neuroendocrine tumours and neuroendocrine carcinomas) and include tumours of variable aggressivity. We consider them together here in this Review owing to similarities in their clinical presentation, pathomechanism and genetic background. No preoperative biomarkers of malignancy are available for several forms of these endocrine tumours. Moreover, biomarkers are also needed for the follow-up of tumour progression (especially in hormonally inactive tumours), prognosis and treatment efficacy monitoring. Circulating blood-borne ncRNAs show promising utility as biomarkers. These ncRNAs, including microRNAs, long non-coding RNAs and circular RNAs, are involved in several aspects of gene expression regulation, and their stability and tissue-specific expression could make them ideal biomarkers. However, no circulating ncRNA biomarkers have yet been introduced into routine clinical practice, which is mostly owing to methodological and standardization problems. In this Review, following a brief synopsis of these endocrine tumours and the biology of ncRNAs, the major research findings, pathomechanisms and methodological questions are discussed along with an outlook for future studies.
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Affiliation(s)
- Henriett Butz
- HUN-REN-SU Hereditary Tumours Research Group, Budapest, Hungary
- Department of Molecular Genetics and the National Tumour Biology Laboratory, National Institute of Oncology, Budapest, Hungary
- Department of Laboratory Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary
| | - Attila Patócs
- HUN-REN-SU Hereditary Tumours Research Group, Budapest, Hungary
- Department of Molecular Genetics and the National Tumour Biology Laboratory, National Institute of Oncology, Budapest, Hungary
- Department of Laboratory Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary
| | - Peter Igaz
- Department of Endocrinology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
- Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
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8
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Yuan J, Yan K, Guo Y, Li Y. MicroRNAs: emerging biomarkers and therapeutic targets in pancreatic cancer. Front Mol Biosci 2024; 11:1457875. [PMID: 39290995 PMCID: PMC11406015 DOI: 10.3389/fmolb.2024.1457875] [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: 07/01/2024] [Accepted: 08/23/2024] [Indexed: 09/19/2024] Open
Abstract
Pancreatic cancer (PC) is a highly malignant disease with high aggressiveness and a dismal prognosis, which is challenging to diagnose clinically early and gains low benefit from standard therapies. MicroRNAs (miRNAs) have become a hot topic in oncology research. Current evidence indicates that miRNAs are regulators involved in the entire process of PC, providing new diagnostic and therapeutic strategies for this fatal disease. Related research has been rapidly updated, making it necessary to review it to propose new directions and ideas and provide guidance for the development of precision medicine for PC. We reviewed the relevant literature through Pubmed, Embase, Web of Science and Medline, showing that abnormally expressed miRNAs in PC patients have the potential to be used as biomarkers for diagnosis and prognosis, highlighting the excellent prospect of combining miRNAs with traditional therapies, and the effective application of these factors for PC, especially miRNA mimics and inhibitors. MiRNAs participate in the entire process of PC and play important roles in diagnosis, treatment and prognosis. They are potential factors in conquering PC in the future.
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Affiliation(s)
- Jiaqian Yuan
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Kaiqi Yan
- Department of Materials Engineering and Science, Ningbo University of Technology, Ningbo, China
| | - Yong Guo
- Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Yan Li
- Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
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Przybyszewski O, Mik M, Nowicki M, Kusiński M, Mikołajczyk-Solińska M, Śliwińska A. Using microRNAs Networks to Understand Pancreatic Cancer-A Literature Review. Biomedicines 2024; 12:1713. [PMID: 39200178 PMCID: PMC11351910 DOI: 10.3390/biomedicines12081713] [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: 05/30/2024] [Revised: 07/26/2024] [Accepted: 07/28/2024] [Indexed: 09/02/2024] Open
Abstract
Pancreatic cancer is a severe disease, challenging to diagnose and treat, and thereby characterized by a poor prognosis and a high mortality rate. Pancreatic ductal adenocarcinoma (PDAC) represents approximately 90% of pancreatic cancer cases, while other cases include neuroendocrine carcinoma. Despite the growing knowledge of the pathophysiology of this cancer, the mortality rate caused by it has not been effectively reduced. Recently, microRNAs have aroused great interest among scientists and clinicians, as they are negative regulators of gene expression, which participate in many processes, including those related to the development of pancreatic cancer. The aim of this review is to show how microRNAs (miRNAs) affect key signaling pathways and related cellular processes in pancreatic cancer development, progression, diagnosis and treatment. We included the results of in vitro studies, animal model of pancreatic cancer and those performed on blood, saliva and tumor tissue isolated from patients suffering from PDAC. Our investigation identified numerous dysregulated miRNAs involved in KRAS, JAK/STAT, PI3/AKT, Wnt/β-catenin and TGF-β signaling pathways participating in cell cycle control, proliferation, differentiation, apoptosis and metastasis. Moreover, some miRNAs (miRNA-23a, miRNA-24, miRNA-29c, miRNA-216a) seem to be engaged in a crosstalk between signaling pathways. Evidence concerning the utility of microRNAs in the diagnosis and therapy of this cancer is poor. Therefore, despite growing knowledge of the involvement of miRNAs in several processes associated with pancreatic cancer, we are beginning to recognize and understand their role and usefulness in clinical practice.
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Affiliation(s)
- Oskar Przybyszewski
- Department of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska St., 92-213 Lodz, Poland
| | - Michał Mik
- Department of General and Colorectal Surgery, Medical University of Lodz, 113 Stefana Żeromskiego St., 90-549 Lodz, Poland; (M.M.); (M.N.)
| | - Michał Nowicki
- Department of General and Colorectal Surgery, Medical University of Lodz, 113 Stefana Żeromskiego St., 90-549 Lodz, Poland; (M.M.); (M.N.)
| | - Michał Kusiński
- Department of Endocrinological, General and Oncological Surgery, Medical University of Lodz, 62 Pabianicka St., 93-513 Lodz, Poland;
| | - Melania Mikołajczyk-Solińska
- Department of Internal Medicine, Diabetology and Clinical Pharmacology, Medical University of Lodz, 251 Pomorska St., 92-213 Lodz, Poland;
| | - Agnieszka Śliwińska
- Department of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska St., 92-213 Lodz, Poland
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Nyirő G, Szeredás BK, Decmann Á, Herold Z, Vékony B, Borka K, Dezső K, Zalatnai A, Kovalszky I, Igaz P. miRNA Expression Profiling in G1 and G2 Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2024; 16:2528. [PMID: 39061169 PMCID: PMC11275009 DOI: 10.3390/cancers16142528] [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: 06/22/2024] [Revised: 07/09/2024] [Accepted: 07/10/2024] [Indexed: 07/28/2024] Open
Abstract
Pancreatic neuroendocrine neoplasms pose a growing clinical challenge due to their rising incidence and variable prognosis. The current study aims to investigate microRNAs (miRNA; miR) as potential biomarkers for distinguishing between grade 1 (G1) and grade 2 (G2) pancreatic neuroendocrine tumors (PanNET). A total of 33 formalin-fixed, paraffin-embedded samples were analyzed, comprising 17 G1 and 16 G2 tumors. Initially, literature-based miRNAs were validated via real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), confirming significant downregulation of miR-130b-3p and miR-106b in G2 samples. Through next-generation sequencing, we have identified and selected the top six miRNAs showing the highest difference between G1 and G2 tumors, which were further validated. RT-qPCR validation confirmed the downregulation of miR-30d-5p in G2 tumors. miRNA combinations were created to distinguish between the two PanNET grades. The highest diagnostic performance in distinguishing between G1 and G2 PanNETs by a machine learning algorithm was achieved when using the combination miR-106b + miR-130b-3p + miR-127-3p + miR-129-5p + miR-30d-5p. The ROC analysis resulted in a sensitivity of 83.33% and a specificity of 87.5%. The findings underscore the potential use of miRNAs as biomarkers for stratifying PanNET grades, though further research is warranted to enhance diagnostic accuracy and clinical utility.
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Affiliation(s)
- Gábor Nyirő
- Department of Endocrinology, Faculty of Medicine, Semmelweis University, Korányi Str. 2/a, 1083 Budapest, Hungary; (G.N.); (B.K.S.); (B.V.)
- Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis University, Korányi Str. 2/a, 1083 Budapest, Hungary
- Department of Laboratory Medicine, Faculty of Medicine, Semmelweis University, Nagyvárad sq. 4., 1089 Budapest, Hungary
| | - Bálint Kende Szeredás
- Department of Endocrinology, Faculty of Medicine, Semmelweis University, Korányi Str. 2/a, 1083 Budapest, Hungary; (G.N.); (B.K.S.); (B.V.)
| | - Ábel Decmann
- Dr. László Vass Health Center, Municipality of District XV, 1152 Budapest, Hungary;
| | - Zoltan Herold
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Baross Str. 23-25, 1082 Budapest, Hungary
| | - Bálint Vékony
- Department of Endocrinology, Faculty of Medicine, Semmelweis University, Korányi Str. 2/a, 1083 Budapest, Hungary; (G.N.); (B.K.S.); (B.V.)
- Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis University, Korányi Str. 2/a, 1083 Budapest, Hungary
| | - Katalin Borka
- Department of Pathology, Forensic and Insurance Medicine, Faculty of Medicine, Semmelweis University, Üllői Str. 93, 1083 Budapest, Hungary;
| | - Katalin Dezső
- Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Üllői Str. 26, 1085 Budapest, Hungary; (K.D.); (A.Z.); (I.K.)
| | - Attila Zalatnai
- Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Üllői Str. 26, 1085 Budapest, Hungary; (K.D.); (A.Z.); (I.K.)
| | - Ilona Kovalszky
- Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Üllői Str. 26, 1085 Budapest, Hungary; (K.D.); (A.Z.); (I.K.)
| | - Peter Igaz
- Department of Endocrinology, Faculty of Medicine, Semmelweis University, Korányi Str. 2/a, 1083 Budapest, Hungary; (G.N.); (B.K.S.); (B.V.)
- Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis University, Korányi Str. 2/a, 1083 Budapest, Hungary
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Franchina M, Cavalcoli F, Falco O, La Milia M, Elvevi A, Massironi S. Biochemical Markers for Neuroendocrine Tumors: Traditional Circulating Markers and Recent Development-A Comprehensive Review. Diagnostics (Basel) 2024; 14:1289. [PMID: 38928704 PMCID: PMC11203125 DOI: 10.3390/diagnostics14121289] [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: 05/08/2024] [Revised: 06/13/2024] [Accepted: 06/15/2024] [Indexed: 06/28/2024] Open
Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms presenting unique challenges in diagnosis and management. Traditional markers such as chromogranin A (CgA), pancreatic polypeptide (PP), and neuron-specific enolase (NSE) have limitations in terms of specificity and sensitivity. Specific circulating markers such as serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and various gastrointestinal hormones such as gastrin, glucagon, somatostatin, and vasoactive intestinal peptide (VIP) have a role in identifying functional NENs. Recent advances in molecular and biochemical markers, also accounting for novel genomic and proteomic markers, have significantly improved the landscape for the diagnosis and monitoring of NENs. This review discusses these developments, focusing on both traditional markers such as CgA and NSE, as well as specific hormones like gastrin, insulin, somatostatin, glucagon, and VIP. Additionally, it covers emerging genomic and proteomic markers that are shaping current research. The clinical applicability of these markers is highlighted, and their role in improving diagnostic accuracy, predicting surgical outcomes, and monitoring response to treatment is demonstrated. The review also highlights the need for further research, including validation of these markers in larger studies, development of standardized assays, and integration with imaging techniques. The evolving field of biochemical markers holds promise for improving patient outcomes in the treatment of NENs, although challenges in standardization and validation remain.
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Affiliation(s)
- Marianna Franchina
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Federica Cavalcoli
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
| | - Olga Falco
- Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy
| | - Marta La Milia
- Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy
| | - Alessandra Elvevi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Sara Massironi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
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Huang J, Gao G, Ge Y, Liu J, Cui H, Zheng R, Wang J, Wang S, Go VL, Hu S, Liu Y, Yang M, Sun Y, Shang D, Tian Y, Zhang Z, Xiang Z, Wang H, Guo J, Xiao GG. Development of a Serum-Based MicroRNA Signature for Early Detection of Pancreatic Cancer: A Multicenter Cohort Study. Dig Dis Sci 2024; 69:1263-1273. [PMID: 38451429 PMCID: PMC11026211 DOI: 10.1007/s10620-024-08338-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 02/05/2024] [Indexed: 03/08/2024]
Abstract
BACKGROUND A grim prognosis of pancreatic cancer (PCa) was attributed to the difficulty in early diagnosis of the disease. AIMS Identifying novel biomarkers for early detection of PCa is thus urgent to improve the overall survival rates of patients. METHODS The study was performed firstly by identification of candidate microRNAs (miRNAs) in formalin-fixed, paraffin-embedded tissues using microarray profiles, and followed by validation in a serum-based cohort study to assess clinical utility of the candidates. In the cohorts, a total of 1273 participants from four centers were retrospectively recruited as two cohorts including training and validation cohort. The collected serum specimens were analyzed by real-time polymerase chain reaction. RESULTS We identified 27 miRNAs expressed differentially in PCa tissues as compared to the benign. Of which, the top-four was selected as a panel whose diagnostic efficacy was fully assessed in the serum specimens. The panel exhibited superior to CA19-9, CA125, CEA and CA242 in discriminating patients with early stage PCa from healthy controls or non-PCa including chronic pancreatitis as well as pancreatic cystic neoplasms, with the area under the curves (AUC) of 0.971 (95% CI 0.956-0.987) and 0.924 (95% CI 0.899-0.949), respectively. Moreover, the panel eliminated interference from other digestive tumors with a specificity of 90.2%. CONCLUSIONS A panel of four serum miRNAs was developed showing remarkably discriminative ability of early stage PCa from either healthy controls or other pancreatic diseases, suggesting it may be developed as a novel, noninvasive approach for early screening of PCa in clinic.
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Affiliation(s)
- Jing Huang
- National Key Laboratory of Fine Chemical Engineering and Department of Pharmacology, School of Chemical Engineering, Dalian University of Technology, Dalian, China
| | - Ge Gao
- Department of Laboratory Medicine, The Second & The Third Xiangya Hospitals, Central South University, Changsha, China
| | - Yang Ge
- Department of Food Safety and Toxicology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianzhou Liu
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hongtu Cui
- School of Biomedical Engineering, Dalian University of Technology, Dalian, China
| | - Ren Zheng
- National Key Laboratory of Fine Chemical Engineering and Department of Pharmacology, School of Chemical Engineering, Dalian University of Technology, Dalian, China
| | - Jialin Wang
- National Key Laboratory of Fine Chemical Engineering and Department of Pharmacology, School of Chemical Engineering, Dalian University of Technology, Dalian, China
| | - Si Wang
- National Key Laboratory of Fine Chemical Engineering and Department of Pharmacology, School of Chemical Engineering, Dalian University of Technology, Dalian, China
| | - Vay Liang Go
- The UCLA Agi Hirshberg Center for Pancreatic Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Shen Hu
- The UCLA Agi Hirshberg Center for Pancreatic Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Yefu Liu
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No.44 Xiaoheyan Road, Dadong District, Shenyang, China
| | - Minwei Yang
- Department of Biliary-Pancreatic Surgery, School of Medicine, Ren Ji Hospital,, Shanghai Jiao Tong University, Shanghai, China
| | - Yongwei Sun
- Department of Biliary-Pancreatic Surgery, School of Medicine, Ren Ji Hospital,, Shanghai Jiao Tong University, Shanghai, China
| | - Dong Shang
- Clinical Laboratory of Integrative Medicine , Department of General Surgery, Pancreaticobiliary Center, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yantao Tian
- Pancreatic and Gastric Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Zhigang Zhang
- State Key Laboratory of Oncogenes and Related Genes, School of Medicine, Ren Ji Hospital, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, China
| | - Zhongyuan Xiang
- Department of Laboratory Medicine, The Second & The Third Xiangya Hospitals, Central South University, Changsha, China
| | | | - Junchao Guo
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Gary Guishan Xiao
- National Key Laboratory of Fine Chemical Engineering and Department of Pharmacology, School of Chemical Engineering, Dalian University of Technology, Dalian, China.
- The UCLA Agi Hirshberg Center for Pancreatic Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
- Functional Genomics and Proteomics Laboratory, Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, USA.
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Bagheri Shirvan S, Shahabinejad M, Mohajertehran F, Nazari N. Evaluation of Mir-1290 as a Possible Diagnostic Factor in the Serum of Oral Squamous Cell Carcinoma Patients with Qualitative Real-Time Polymerase Chain Reaction. IRANIAN JOURNAL OF PATHOLOGY 2024; 19:244-249. [PMID: 39118790 PMCID: PMC11304459 DOI: 10.30699/ijp.2024.2010130.3161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 12/22/2023] [Indexed: 08/10/2024]
Abstract
Background & Objective This study aimed to determine the incidence of microRNA (miRNA; miR-1290) in the serum of oral squamous cell carcinoma (OSCC) patients compared to a control group using the qualitative real-time polymerase chain reaction (PCR) method. Methods Blood serum samples were obtained from patients diagnosed with OSCC and confirmed through biopsy. The samples were collected from patients referred to the Mashhad Dental Faculty and Ghaem Hospital. The OSCC group consisted of 17 patients, while the healthy group included 15 individuals. RNA was extracted from the patient samples, and samples with an A260/280 ratio between 1.8 and 2.0 (indicating acceptable RNA quality) were immediately converted into complementary DNA (cDNA) using albumin and cDNA reference genes. The SYBR green real-time reverse transcriptase PCR method was used to measure the presence of miR-1290 in the blood samples. Results A total of 32 patients were examined in this study, including 17 women (53.1%) and 15 men (46.9%). The mean age was 46.7 years in the healthy group and 54.6 years in the SCC group, indicating a significant difference (P<0.05). The expression level of the miR-1290 gene was higher in patients with SCC compared to the healthy group (P=0.000). While the expression level of miR-1290 was higher in grade 3 and advanced stage than in grades 2 and 1 and early stage, the differences were not statistically significant (P=0.173 and P=0.564 for grade and stage, respectively). Conclusion The expression level of miR-1290 may increase in SCC patients compared to healthy individuals, making it a potential circulating biomarker. Further investigations for diagnostic utility would be warranted.
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Affiliation(s)
- Siavash Bagheri Shirvan
- Student Research Committee, Faculty of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mehdi Shahabinejad
- Oral and Maxillofacial Pathology Department, Oral and Maxillofacial Diseases Research Center, Faculty of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farnaz Mohajertehran
- Oral and Maxillofacial Pathology Department, Oral and Maxillofacial Diseases Research Center, Faculty of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran
- Oral and Maxillofacial Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nazanin Nazari
- Student Research Committee, Faculty of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran
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Zhang T, Xie Z, Zheng X, Liang Y, Lu Y, Zhong H, Qian F, Zhu Y, Sun R, Sheng Y, Hu J. CRISPR-Cas12a powered hybrid nanoparticle for extracellular vesicle aggregation and in-situ microRNA detection. Biosens Bioelectron 2024; 245:115856. [PMID: 37995623 DOI: 10.1016/j.bios.2023.115856] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 11/08/2023] [Accepted: 11/15/2023] [Indexed: 11/25/2023]
Abstract
Efficient extracellular vesicle (EV) enrichment and timely internal RNA detection for cancer diagnostics are highly desirable and remain a challenge. Here, we report a rapid EV aggregation induced in-situ microRNA detection technology based on cationic lipid-polymer hybrid nanoparticles encapsulating cascade system of catalytic hairpin assembly and CRISPR-Cas12a (CLHN-CCC), allowing for EV enrichment in three-dimensional space and in-situ detection of internal microRNAs in one step within 30 min. The enrichment efficiency (>90%) of CLHN-CCC is demonstrated in artificial EVs, cell-secreted EVs and serum EVs, which is 5-fold higher than that of traditional ultracentrifugation. The sensitive detection of artificial EVs and internal miR-1290 was achieved with the limit of detection of 10 particles/μL and 0.07 amol, respectively. After lyophilization, CLHN-CCC shows no obvious loss of performance within 6 months, making it much more robust and user friendly. This technique could sensitively (sensitivity = 92.9%) and selectively (selectivity = 85.7%) identify low amount miR-1290 in serum EVs, distinguishing early-stage pancreatic cancer patients from healthy subjects, showing high potential for clinical applications.
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Affiliation(s)
- Tenghua Zhang
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China
| | - Zihui Xie
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China
| | - Xiaohe Zheng
- Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Yuxin Liang
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China
| | - Yao Lu
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China
| | - Hankang Zhong
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China
| | - Feiyang Qian
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China
| | - Yuqing Zhu
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China
| | - Ruiting Sun
- National Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510030, China
| | - Yan Sheng
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.
| | - Jiaming Hu
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.
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Stosic K, Senar OA, Tarfouss J, Bouchart C, Navez J, Van Laethem JL, Arsenijevic T. A Comprehensive Review of the Potential Role of Liquid Biopsy as a Diagnostic, Prognostic, and Predictive Biomarker in Pancreatic Ductal Adenocarcinoma. Cells 2023; 13:3. [PMID: 38201207 PMCID: PMC10778087 DOI: 10.3390/cells13010003] [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: 10/30/2023] [Revised: 12/13/2023] [Accepted: 12/15/2023] [Indexed: 01/12/2024] Open
Abstract
Pancreatic ductal adenocarcinoma is one of the most lethal malignant diseases, with a mortality rate being close to incidence. Due to its heterogeneity and plasticity, as well as the lack of distinct symptoms in the early phases, it is very often diagnosed at an advanced stage, resulting in poor prognosis. Traditional tissue biopsies remain the gold standard for making a diagnosis, but have an obvious disadvantage in their inapplicability for frequent sampling. Blood-based biopsies represent a non-invasive method which potentially offers easy and repeated sampling, leading to the early detection and real-time monitoring of the disease and hopefully an accurate prognosis. Given the urgent need for a reliable biomarker that can estimate a patient's condition and response to an assigned treatment, blood-based biopsies are emerging as a potential new tool for improving patients' survival and surveillance. In this article, we discuss the current advances and challenges in using liquid biopsies for pancreatic cancer, focusing on circulating tumour DNA (ctDNA), extracellular vesicles (EVs), and circulating tumour cells (CTCs), and compare the performance and reliability of different biomarkers and combinations of biomarkers.
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Affiliation(s)
- Kosta Stosic
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, 1070 Brussels, Belgium (O.A.S.); (C.B.)
| | - Oier Azurmendi Senar
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, 1070 Brussels, Belgium (O.A.S.); (C.B.)
| | - Jawad Tarfouss
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, 1070 Brussels, Belgium (O.A.S.); (C.B.)
| | - Christelle Bouchart
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, 1070 Brussels, Belgium (O.A.S.); (C.B.)
- Department of Radiation Oncology, Hopital Universitaire de Bruxelles (H.U.B.), Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium
| | - Julie Navez
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, 1070 Brussels, Belgium (O.A.S.); (C.B.)
- Department of Hepato-Biliary-Pancreatic Surgery, Hopital Universitaire de Bruxelles (H.U.B.), Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium
| | - Jean-Luc Van Laethem
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, 1070 Brussels, Belgium (O.A.S.); (C.B.)
- Department of Gastroenterology, Hepatology and Digestive Oncology, Hopital Universitaire de Bruxelles (H.U.B.), Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium
| | - Tatjana Arsenijevic
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, 1070 Brussels, Belgium (O.A.S.); (C.B.)
- Department of Gastroenterology, Hepatology and Digestive Oncology, Hopital Universitaire de Bruxelles (H.U.B.), Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium
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Capik O, Gundogdu B, Tatar A, Sahin A, Chen F, Creighton CJ, Karatas OF. Oncogenic miR-1825 promotes head and neck carcinogenesis via targeting FREM1. J Cell Biochem 2023; 124:1628-1645. [PMID: 37683055 DOI: 10.1002/jcb.30473] [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: 04/24/2023] [Revised: 07/26/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023]
Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant cancer type worldwide. Although the therapeutic modalities currently used for patients with HNSCC improved in recent decades, HNSCC prognosis is still poor. Therefore, it is an urgent necessity to understand the pathogenesis of HNSCC, to develop novel and effective treatment strategies, and to characterize and identify the oncogenes that are responsible for an aggressive HNSCC phenotype. In this study, we aimed to better understand the roles of miR-1825 in the pathogenesis of HNSCC. We examined the impacts of miR-1825 deregulation on the cancer-associated phenotypes using in vitro tests evaluating cell viability, clonogenicity, cell migration, invasion, apoptosis, and stem cell characteristics. In addition, we investigated the effects of miR-1825 overexpression on the tumor formation capacity of head and neck cancer cells in vivo using nude mice. We searched for potential targets of miR-1825 using microarray analysis and luciferase assay. We found that miR-1825 expression is upregulated in head and neck cells and clinical tumor samples in comparison to corresponding controls, where it potentially acts as an oncogene. We, then, showed that ectopic miR-1825 overexpression promotes cellular phenotypes related to head and neck cancer progression in vitro and has a stimulating potential on cancer formation in vivo. We also identified FREM1 as a direct target of miR-1825 and demonstrated its reduced expression in HNSCC samples using immunohistochemistry analysis. Collectively, we suggest that the miR-1825/FREM1 axis serves as an important mediator of HNSCC development, where miR-1825 acts as an oncogene.
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Affiliation(s)
- Ozel Capik
- Molecular Biology and Genetics Department, Erzurum Technical University, Erzurum, Turkey
- Molecular Cancer Biology Laboratory, High Technology Application and Research Center, Erzurum Technical University, Erzurum, Turkey
| | - Betul Gundogdu
- Department of Medical Pathology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
| | - Arzu Tatar
- Department of Otorhinolaryngology Diseases, Faculty of Medicine, Ataturk University, Erzurum, Turkey
| | - Abdulkadir Sahin
- Department of Otorhinolaryngology Diseases, Faculty of Medicine, Ataturk University, Erzurum, Turkey
| | - Fengju Chen
- Department of Medicine and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA
| | - Chad J Creighton
- Department of Medicine and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA
| | - Omer Faruk Karatas
- Molecular Biology and Genetics Department, Erzurum Technical University, Erzurum, Turkey
- Molecular Cancer Biology Laboratory, High Technology Application and Research Center, Erzurum Technical University, Erzurum, Turkey
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Khan IA, Saraya A. Circulating MicroRNAs as Noninvasive Diagnostic and Prognostic Biomarkers in Pancreatic Cancer: A Review. J Gastrointest Cancer 2023; 54:720-730. [PMID: 36322366 DOI: 10.1007/s12029-022-00877-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/19/2022] [Indexed: 11/05/2022]
Abstract
Pancreatic cancer (PC) is one of the most lethal human cancers. Currently, most PC cases are diagnosed at an already advanced stage. Early detection of PC is critical to improving survival rates. Therefore, there is an urgent need to identify biomarkers for the early detection of PC. Recently, circulating miRNAs in whole blood and other body fluids have been reported as promising biomarkers for the early detection of various cancers, including PC. Furthermore, due to minimal invasiveness and technical availability, circulating miRNAs hold promise for further wide usage. As a potential novel molecular marker, circulating miRNAs not only represent promising noninvasive diagnostic and prognostic tools but could also improve the evaluation of tumor classification, metastasis, and curative effect. The purpose of this review is to outline the available information regarding circulating miRNAs as biomarkers for the early detection of PC.
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Affiliation(s)
- Imteyaz Ahmad Khan
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
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Bevere M, Masetto F, Carazzolo ME, Bettega A, Gkountakos A, Scarpa A, Simbolo M. An Overview of Circulating Biomarkers in Neuroendocrine Neoplasms: A Clinical Guide. Diagnostics (Basel) 2023; 13:2820. [PMID: 37685358 PMCID: PMC10486716 DOI: 10.3390/diagnostics13172820] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/14/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous group of diseases that are characterized by different behavior and clinical manifestations. The diagnosis and management of this group of tumors are challenging due to tumor complexity and lack of precise and widely validated biomarkers. Indeed, the current circulating mono-analyte biomarkers (such as chromogranin A) are ineffective in describing such complex tumors due to their poor sensitivity and specificity. In contrast, multi-analytical circulating biomarkers (including NETest) are emerging as more effective tools to determine the real-time profile of the disease, both in terms of accurate diagnosis and effective treatment. In this review, we will analyze the capabilities and limitations of different circulating biomarkers focusing on three relevant questions: (1) accurate and early diagnosis; (2) monitoring of disease progression and response to therapy; and (3) detection of early relapse.
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Affiliation(s)
- Michele Bevere
- ARC-Net Research Center, University of Verona, 37134 Verona, Italy; (M.B.); (F.M.); (A.G.); (A.S.)
| | - Francesca Masetto
- ARC-Net Research Center, University of Verona, 37134 Verona, Italy; (M.B.); (F.M.); (A.G.); (A.S.)
| | - Maria Elena Carazzolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy; (M.E.C.); (A.B.)
| | - Alice Bettega
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy; (M.E.C.); (A.B.)
| | - Anastasios Gkountakos
- ARC-Net Research Center, University of Verona, 37134 Verona, Italy; (M.B.); (F.M.); (A.G.); (A.S.)
| | - Aldo Scarpa
- ARC-Net Research Center, University of Verona, 37134 Verona, Italy; (M.B.); (F.M.); (A.G.); (A.S.)
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy; (M.E.C.); (A.B.)
| | - Michele Simbolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy; (M.E.C.); (A.B.)
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Kordaß T, Chao TY, Osen W, Eichmüller SB. Novel microRNAs modulating ecto-5'-nucleotidase expression. Front Immunol 2023; 14:1199374. [PMID: 37409119 PMCID: PMC10318900 DOI: 10.3389/fimmu.2023.1199374] [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: 04/03/2023] [Accepted: 06/02/2023] [Indexed: 07/07/2023] Open
Abstract
Introduction The expression of immune checkpoint molecules (ICMs) by cancer cells is known to counteract tumor-reactive immune responses, thereby promoting tumor immune escape. For example, upregulated expression of ecto-5'-nucleotidase (NT5E), also designated as CD73, increases extracellular levels of immunosuppressive adenosine, which inhibits tumor attack by activated T cells. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Thus, the binding of miRNAs to the 3'-untranslated region of target mRNAs either blocks translation or induces degradation of the targeted mRNA. Cancer cells often exhibit aberrant miRNA expression profiles; hence, tumor-derived miRNAs have been used as biomarkers for early tumor detection. Methods In this study, we screened a human miRNA library and identified miRNAs affecting the expression of ICMs NT5E, ENTPD1, and CD274 in the human tumor cell lines SK-Mel-28 (melanoma) and MDA-MB-231 (breast cancer). Thereby, a set of potential tumor-suppressor miRNAs that decreased ICM expression in these cell lines was defined. Notably, this study also introduces a group of potential oncogenic miRNAs that cause increased ICM expression and presents the possible underlying mechanisms. The results of high-throughput screening of miRNAs affecting NT5E expression were validated in vitro in 12 cell lines of various tumor entities. Results As result, miR-1285-5p, miR-155-5p, and miR-3134 were found to be the most potent inhibitors of NT5E expression, while miR-134-3p, miR-6859-3p, miR-6514-3p, and miR-224-3p were identified as miRNAs that strongly enhanced NT5E expression levels. Discussion The miRNAs identified might have clinical relevance as potential therapeutic agents and biomarkers or therapeutic targets, respectively.
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Affiliation(s)
- Theresa Kordaß
- GMP & T Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Faculty of Biosciences, University Heidelberg, Heidelberg, Germany
| | - Tsu-Yang Chao
- GMP & T Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Wolfram Osen
- GMP & T Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Stefan B. Eichmüller
- GMP & T Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Anoop TM, Basu PK, Chandramohan K, Thomas A, Manoj S. Evolving utility of exosomes in pancreatic cancer management. World J Methodol 2023; 13:46-58. [PMID: 37456979 PMCID: PMC10348087 DOI: 10.5662/wjm.v13.i3.46] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 05/02/2023] [Accepted: 05/31/2023] [Indexed: 06/20/2023] Open
Abstract
Despite the development of newer oncological treatment, the survival of patients with pancreatic cancer (PC) remains poor. Recent studies have identified exosomes as essential mediators of intercellular communications and play a vital role in tumor initiation, metastasis and chemoresistance. Thus, the utility of liquid biopsies using exosomes in PC management can be used for early detection, diagnosis, monitoring as well as drug delivery vehicles for cancer therapy. This review summarizes the function, and clinical applications of exosomes in cancers as minimally invasive liquid biomarker in diagnostic, prognostic and therapeutic roles.
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Affiliation(s)
- Thattungal Manoharan Anoop
- Department of Medical Oncology, Regional Cancer Center, Medical College Campus, Thiruvananthapuram 695011, Kerala, India
| | - Palash Kumar Basu
- Department of Avionics, Indian Institute of Space Science & Technology (IIST), Thiruvananthapuram 695547, Kerala, India
| | - K Chandramohan
- Surgical Oncology, Regional Cancer Center, Thiruvananthapuram 695011, Kerala, India
| | - Ajai Thomas
- Department of Medical Oncology, Regional Cancer Center, Medical College Campus, Thiruvananthapuram 695011, Kerala, India
| | - S Manoj
- Department of Medical Oncology, Regional Cancer Center, Medical College Campus, Thiruvananthapuram 695011, Kerala, India
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21
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A circulating microRNA panel as a novel dynamic monitor for oral squamous cell carcinoma. Sci Rep 2023; 13:2000. [PMID: 36737651 PMCID: PMC9898506 DOI: 10.1038/s41598-023-28550-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 01/19/2023] [Indexed: 02/05/2023] Open
Abstract
Oral squamous cell carcinoma (OSCC) has high recurrence and mortality rates despite advances in diagnosis and treatment. Therefore, it is necessary to identify new biomarkers for early detection, efficient monitoring, and prognosis prediction. Since microRNA (miRNA) is stable and detectable in serum, it has been reported to inform the diagnosis and monitor disease progression through liquid biopsy. In this study, a circulating specific miRNA panel in OSCC patients was developed, and its usefulness as a dynamic monitor was validated. Small RNAs were extracted from the serum of OSCC patients (n = 4) and normal controls (n = 6) and profiled using next-generation sequencing. NGS identified 42 differentially expressed miRNAs (DEmiRNAs) in serum between patients with OSCC and healthy controls, with threefold differences (p < 0.05). Combining the 42 DEmiRNAs and The Cancer Genome Atlas (TCGA) databases OSCC cohort, 9 overlapping DEmiRNAs were screened out. Finally, 4 significantly up-regulated miRNAs (miR-92a-3p, miR-92b-3p, miR-320c and miR-629-5p) were identified from OSCC patients via validation in the Chungnam National University Hospital cohort. Application of the specific miRNA panel for distinguishing OSCC patients from healthy controls produced specificity and sensitivity of 97.8 and 74%, respectively. In addition, the serum levels of these 4 miRNAs significantly decreased after complete surgical resection and increased after recurrence. We suggest that circulating 4-miRNA panel might be promising non-invasive predictors for diagnosing and monitoring the progression of patients with OSCC.
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22
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Bhattacharya A. Epigenetic modifications and regulations in gastrointestinal diseases. EPIGENETICS IN ORGAN SPECIFIC DISORDERS 2023:497-543. [DOI: 10.1016/b978-0-12-823931-5.00005-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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23
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Sharma N, Srivastava S. Diagnosis of Pancreatic Cancer Using miRNA30e Biosensor. Interdiscip Sci 2022; 14:804-813. [PMID: 35781212 DOI: 10.1007/s12539-022-00531-1] [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: 12/02/2021] [Revised: 05/27/2022] [Accepted: 06/01/2022] [Indexed: 06/15/2023]
Abstract
This work describes miRNA-based electrochemical biosensor for detection of miRNA30e, a pancreatic cancer biomarker. The screen-printed gold electrode was functionalized using cysteine hydrochloride followed by immobilization of synthesized colloidal gold nanorods (10-12 nm diameter and 25-65 nm length). The gold nanorods modified electrode surface was amino functionalized for covalent attachment of single-stranded DNA probe against miRNA30e (miR30e). This platform was utilized for electrochemical measurements and response analysis of target miRNA30e. Electrochemical impedance spectroscopic measurements showed very poor sensitivity (13.51 Ω/µg/mL/cm2) using charge transfer resistance calibration plots. Cyclic voltammetry and differential pulse voltammetry-based miR30e quantification showed decreasing current response with increasing concentration of miR30e with detection range of 0.1 fg/mL-0.1 µg/mL (14.9 aM-14.9 nM). The sensitivity of DPV sensing (104.4 µA/µg/mL/cm2) was found to be 1.3 times higher than that of CV-based quantification (79.6 µA/µg/mL/cm2). miRNA-based biosensors have the potential of replacing current invasive, time consuming and technically difficult diagnostic procedures. Furthermore, the lower limit of detection of 14.9 aM miRNA30e makes it a promising tool for detection of cancer at early stages and hence increasing survival rate.
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Affiliation(s)
- Namita Sharma
- Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, Noida, UP, India
| | - Sudha Srivastava
- Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, Noida, UP, India.
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24
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Nakamura K, Hernández G, Sharma GG, Wada Y, Banwait JK, González N, Perea J, Balaguer F, Takamaru H, Saito Y, Toiyama Y, Kodera Y, Boland CR, Bujanda L, Quintero E, Goel A. A Liquid Biopsy Signature for the Detection of Patients With Early-Onset Colorectal Cancer. Gastroenterology 2022; 163:1242-1251.e2. [PMID: 35850198 PMCID: PMC9613521 DOI: 10.1053/j.gastro.2022.06.089] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/18/2022] [Accepted: 06/27/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Early-onset colorectal cancer (EOCRC) is a distinct clinical and molecular entity with poor survival outcomes compared with late-onset CRC. Although the incidence of EOCRC is rising, current CRC screening strategies have several limitations in diagnostic performance for EOCRC. In view of this clinical challenge, novel and robust biomarkers for detection of EOCRC are necessary. The aim of this study was to develop a circulating micro RNA (miRNA) signature for the diagnosis of patients with EOCRC. METHODS A systematic discovery approach by analyzing a large, publicly available, noncoding RNA expression profiling dataset (GSE115513) was used. A panel of miRNAs was identified, which was subsequently validated in blood samples from patients with EOCRC in 2 independent cohorts (n = 149) compared with controls (n = 110) and pre/postoperative plasma specimens (n = 22) using quantitative reverse-transcription polymerase chain reaction assays. RESULTS In the discovery phase, 4 miRNAs were found to be expressed in blood samples. A combination signature of these 4 miRNAs (miR-193a-5p, miR-210, miR-513a-5p, and miR-628-3p) yielded an area under the curve of 0.92 (95% confidence interval, 0.85-0.96) for identification of EOCRC in the training cohort. The miRNA panel performance was then confirmed in an independent validation cohort (area under the curve, 0.88; 95% confidence interval, 0.82-0.93). Moreover, the miRNA panel robustly identified patients with early-stage EOCRC (P < .001). The decreased expression of miRNAs in postsurgery plasma specimens indicated their tumor specificity. CONCLUSIONS Our novel miRNA signature for the diagnosis of EOCRC has the potential to identify patients with EOCRC with high accuracy for clinical application in the noninvasive diagnosis of EOCRC.
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Affiliation(s)
- Kota Nakamura
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, California; Department of Surgery, Nara Medical University, Nara, Japan
| | - Goretti Hernández
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas; Gastroenterology Department, Hospital Universitario de Canarias, Instituto Universitario de Tecnologías Biomédicas (ITB) and Centro de Investigación Biomédica de Canarias (CIBICAN), Departamento de Medicina Interna, Universidad de La Laguna, Santa Cruz de Tenerife, Tenerife, Spain
| | - Geeta G Sharma
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, California
| | - Yuma Wada
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, California; Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas
| | - Jasjit K Banwait
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas
| | - Natalia González
- Gastroenterology Department, Hospital Universitario de Canarias, Instituto Universitario de Tecnologías Biomédicas (ITB) and Centro de Investigación Biomédica de Canarias (CIBICAN), Departamento de Medicina Interna, Universidad de La Laguna, Santa Cruz de Tenerife, Tenerife, Spain
| | - Jose Perea
- Department of Surgery, Fundación Jiménez Díaz University Hospital, Madrid, Spain; Fundación Jiménez Díaz University Hospital Health Research Institute, Madrid, Spain
| | - Francesc Balaguer
- Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | | | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yuji Toiyama
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - C Richard Boland
- Division of Gastroenterology, School of Medicine, University of California San Diego, La Jolla, California
| | - Luis Bujanda
- Gastroenterology Department, Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain
| | - Enrique Quintero
- Gastroenterology Department, Hospital Universitario de Canarias, Instituto Universitario de Tecnologías Biomédicas (ITB) and Centro de Investigación Biomédica de Canarias (CIBICAN), Departamento de Medicina Interna, Universidad de La Laguna, Santa Cruz de Tenerife, Tenerife, Spain
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, California; Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas; City of Hope Comprehensive Cancer Center, Duarte, California.
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25
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Kalantari S, Kazemi B, Roudi R, Zali H, D'Angelo A, Mohamadkhani A, Madjd Z, Pourshams A. RNA-sequencing for transcriptional profiling of whole blood in early stage and metastatic pancreatic cancer patients. Cell Biol Int 2022; 47:238-249. [PMID: 36229929 DOI: 10.1002/cbin.11924] [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: 08/17/2022] [Accepted: 09/21/2022] [Indexed: 11/10/2022]
Abstract
We investigated the transcriptional profile of whole blood in early and metastatic stages of pancreatic cancer (PaC) patients to identify potential diagnostic factors for early diagnosis. Blood samples from 18 participants (6 healthy individuals, 6 patients in early stage (I/II) PaC, and 6 patients in metastatic PaC) were analyzed by RNA-sequencing. The expression levels of identified genes were subsequently compared with their expression in pancreatic tumor tissues based on TCGA data reported in UALCAN and GEPIA2 databases. Overall, 331 and 724 genes were identified as differentially expressed genes in early and metastatic stages, respectively. Of these, 146 genes were shared by early and metastatic stages. Upregulation of PTCD3 and UBA52 genes and downregulation of A2M and ARID1B genes in PaC patients were observed from early stage to metastasis. TCGA database showed increasing trend in expression levels of these genes from stage I to IV in pancreatic tumor tissue. Finally, we found that low expression of PTCD3, A2M, and ARID1B genes and high expression of UBA52 gene were positively correlated with PaC patients survival. We identified a four-gene set (PTCD3, UBA52, A2M, and ARID1B) expressed in peripheral blood of early stage and metastatic PaC patients that may be useful for PaC early diagnosis.
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Affiliation(s)
- Sima Kalantari
- Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bahram Kazemi
- Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Raheleh Roudi
- Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Hakimeh Zali
- Proteomics Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran.,Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alberto D'Angelo
- Department of Biology and Biochemistry, University of Bath, Bath, UK
| | - Ashraf Mohamadkhani
- Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Madjd
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Akram Pourshams
- Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.,Digestive Oncology Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
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26
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Shen X, Wang X, Lu X, Zhao Y, Guan W. Molecular biology of pancreatic neuroendocrine tumors: From mechanism to translation. Front Oncol 2022; 12:967071. [PMID: 36248960 PMCID: PMC9554633 DOI: 10.3389/fonc.2022.967071] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Accepted: 09/12/2022] [Indexed: 11/13/2022] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are a group of heterogeneous tumors originated from progenitor cells. As these tumors are predominantly non-functional, most of them display asymptomatic characteristics, making it difficult to be realized from early onset. Therefore, patients with pNETs are usually diagnosed with metastatic disease or at a late disease stage. The relatively low incidence also limits our understanding of the biological background of pNETs, which largely impair the development of new effective drugs. The fact that up to 10% of pNETs develop in patients with genetic syndromes have promoted researchers to focus on the gene mutations and driver mutations in MEN1, DAXX/ATRX and mTOR signaling pathway genes have been implicated in disease development and progression. Recent advances in sequencing technologies have further enriched our knowledge of the complex molecular landscape of pNETs, pointing out crucial roles of genes in DNA damage pathways, chromosomal and telomere alterations and epigenetic dysregulation. These novel findings may not only benefit early diagnosis of pNETs, but also help to uncover tumor heterogeneity and shape the future of translational medical treatment. In this review, we focus on the current molecular biology of pNETs and decipher how these findings may translate into future development of targeted therapy.
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Affiliation(s)
- Xiaofei Shen
- Department of General Surgery, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Xingzhou Wang
- Department of General Surgery, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Xiaofeng Lu
- Department of General Surgery, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Yang Zhao
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- *Correspondence: Wenxian Guan, ; Yang Zhao,
| | - Wenxian Guan
- Department of General Surgery, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
- *Correspondence: Wenxian Guan, ; Yang Zhao,
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27
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Cui J, Wang X, Chen S. Ho2O3-TiO2 Nanobelts Electrode for Highly Selective and Sensitive Detection of Cancer miRNAs. BIOSENSORS 2022; 12:bios12100800. [PMID: 36290936 PMCID: PMC9599087 DOI: 10.3390/bios12100800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 08/30/2022] [Accepted: 09/22/2022] [Indexed: 11/16/2022]
Abstract
The design and engineering of effective electrode materials is critical in the development of electrochemical sensors. In the present study, Ho2O3-TiO2 nanobelts were synthesized by an alkaline hydrothermal process. The structure and morphology were investigated by X-ray diffraction (XRD) and field emission scanning electron microscope (FESEM) measurements. The Ho2O3-TiO2 nanobelts showed a distinctly enhanced (004) reflection peak and rough surfaces and were used for the electrochemical selective sensing of various cancer miRNAs, such as prostate cancer miR-141, osteosarcoma miR-21, and pancreatic cancer miR-1290. Voltammetric measurements showed an oxidation peak at +0.4, +0.2, and +1.53 V for the three different cancer biomarkers, respectively, with the detection limit as low as 4.26 aM. The results suggest that the Ho2O3-TiO2 nanobelts can be used as active materials to detect early cancers, for in vitro screening of anticancer drugs, and molecular biology research.
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Affiliation(s)
- Jingjie Cui
- School of Automation, Hangzhou Dianzi University, Hangzhou 310018, China
- Correspondence: ; Tel.: +86-57186878667
| | - Xuping Wang
- School of Automation, Hangzhou Dianzi University, Hangzhou 310018, China
| | - Shaowei Chen
- Department of Chemistry and Biochemistry, University of California, 1156 High Street, Santa Cruz, CA 95064, USA
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28
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Qian Y, Gong Y, Luo G, Liu Y, Wang R, Zou X, Deng S, Lin X, Chen Y, Wang X, Yu X, Cheng H, Liu C. Carbohydrate antigen 125 supplements carbohydrate antigen 19-9 for the prediction of invasive intraductal papillary mucinous neoplasms of the pancreas. World J Surg Oncol 2022; 20:310. [PMID: 36155113 PMCID: PMC9511782 DOI: 10.1186/s12957-022-02720-0] [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: 04/07/2022] [Accepted: 07/26/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Intraductal papillary mucinous neoplasms (IPMNs) are characterized by their abundant mucin production and malignant potential. IPMNs of the pancreas are mainly managed according to their radiographic indications, but this approach lacks accuracy with regard to IPMN grading. Therefore, serological biomarkers such as CA19-9 and CA125 (MUC16) should be employed to assist in predicting the invasiveness of IPMNs. METHODS We investigated the preoperative serum levels of CA19-9, CA125 and CEA in 381 surgical patients with a definite pathological diagnosis of IPMN from July 2010 to December 2019 at the Shanghai Cancer Center. We calculated the Youden indices of each point on the receiver operating characteristic (ROC) curves to identify the most appropriate cut-off values of CA19-9, CA125 and CEA for recognizing malignant IPMNs. Serological biomarker differences were correlated with clinicopathological features of IPMNs, and diagnostic indices of different scenarios were calculated to find the optimum strategy. RESULTS The malignant group had higher serum levels of CA19-9, CA125 and CEA. According to the ROC curves, the cut-off values of CA19-9, CA125 and CEA were readjusted to 38.3 U/ml, 13.4 U/ml and 5.3 μg/L. CA19-9 elevation was significantly associated with vascular invasion and perineural infiltration. CA125 showed good efficacy in predicting invasive IPMN in the CA19-9-negative subgroup. CONCLUSIONS Serological biomarkers are useful and sensitive indicators for recognizing invasive IPMNs. CA19-9 is the most important diagnostic index among all routinely measured serum biomarkers for differentiating malignant from benign IPMNs. CA19-9 should be combined with CA125 to enable more accurate predictions of IPMN malignancy.
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Affiliation(s)
- Yunzhen Qian
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Yitao Gong
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Guopei Luo
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Yu Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Ruijie Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Xuan Zou
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Shengming Deng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Xuan Lin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Yusheng Chen
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Xu Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - He Cheng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
| | - Chen Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
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Komarnicki P, Musiałkiewicz J, Stańska A, Maciejewski A, Gut P, Mastorakos G, Ruchała M. Circulating Neuroendocrine Tumor Biomarkers: Past, Present and Future. J Clin Med 2022; 11:5542. [PMID: 36233409 PMCID: PMC9570647 DOI: 10.3390/jcm11195542] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/12/2022] [Accepted: 09/19/2022] [Indexed: 11/17/2022] Open
Abstract
Neuroendocrine tumors are a heterogeneous group of neoplasms originating from the diffuse endocrine system. Depending on primary location and hormonal status, they range in terms of clinical presentation, prognosis and treatment. Functional tumors often develop symptoms indicating an excess of hormones produced by the neoplasm (exempli gratia insulinoma, glucagonoma and VIPoma) and can be diagnosed using monoanalytes. For non-functional tumors (inactive or producing insignificant amounts of hormones), universal biomarkers have not been established. The matter remains an important unmet need in the field of neuroendocrine tumors. Substances researched over the years, such as chromogranin A and neuron-specific enolase, lack the desired sensitivity and specificity. In recent years, the potential use of Circulating Tumor Cells or multianalytes such as a circulating microRNA and NETest have been widely discussed. They offer superior diagnostic parameters in comparison to traditional biomarkers and depict disease status in a more comprehensive way. Despite a lot of promise, no international standards have yet been developed regarding their routine use and clinical application. In this literature review, we describe the analytes used over the years and cover novel biomarkers that could find a use in the future. We discuss their pros and cons while showcasing recent advances in the field of neuroendocrine tumor biomarkers.
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Affiliation(s)
- Paweł Komarnicki
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznań, Poland
| | - Jan Musiałkiewicz
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznań, Poland
| | - Alicja Stańska
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznań, Poland
| | - Adam Maciejewski
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznań, Poland
| | - Paweł Gut
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznań, Poland
| | - George Mastorakos
- Unit of Endocrinology, Diabetes Mellitus and Metabolism, Aretaieion University Hospital, Medical School, National and Kapodistrian University of Athens, 157 72 Athens, Greece
| | - Marek Ruchała
- Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznań, Poland
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Pancreatic Incidentaloma. J Clin Med 2022; 11:jcm11164648. [PMID: 36012893 PMCID: PMC9409921 DOI: 10.3390/jcm11164648] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 08/03/2022] [Accepted: 08/08/2022] [Indexed: 11/16/2022] Open
Abstract
Pancreatic incidentalomas (PIs) represent a clinical entity increasingly recognized due to advances in and easier access to imaging techniques. By definition, PIs should be detected during abdominal imaging performed for indications other than a pancreatic disease. They range from small cysts to invasive cancer. The incidental diagnosis of pancreatic cancer can contribute to early diagnosis and treatment. On the other hand, inadequate management of PIs may result in overtreatment and unneeded morbidity. Therefore, there is a strong need to evaluate the nature and clinical features of individual PIs. In this review, we summarize the major characteristics related to PIs and present suggestions for their management.
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Phaseolus vulgaris Erythroagglutinin (PHA-E)-Positive Ceruloplasmin Acts as a Potential Biomarker in Pancreatic Cancer Diagnosis. Cells 2022; 11:cells11152453. [PMID: 35954297 PMCID: PMC9367852 DOI: 10.3390/cells11152453] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 07/31/2022] [Accepted: 08/02/2022] [Indexed: 11/17/2022] Open
Abstract
Pancreatic cancer (PC) remains one of the top 10 causes of cancer-related death in recent years. Approximately 80% of PC patients are diagnosed at the middle or advanced stage and miss the opportunity for surgery. The demand for early diagnostic methods and reliable biomarkers is increasing, although a number of tumor markers such as CA19-9 and CEA have already been utilized in clinics. In this study, we analyzed the alteration of N-glycan of serum glycoproteins by mass spectrometry and lectin blotting. The results showed that bisecting GlcNAc structures of glycoproteins are significantly increased in PC patients' sera. With Phaseolus vulgaris Erythroagglutinin (PHA-E) lectin that specifically recognizes bisecting GlcNAc N-glycans, the serum glycoproteins bearing bisecting GlcNAc in PC patients' sera were pulled down and identified by nano-LC-MS/MS. Among them, ceruloplasmin (Cp) was screened out with a satisfied sensitivity and specificity in identifying PC from acute pancreatitis patients (AUC: 0.757) and normal healthy persons (AUC: 0.972), suggesting a close association between Cp and PC development and diagnosis. To prove that, the Cp expression in tumor tissues of PC patients was examined. The results showed that Cp was significantly upregulated in PC tissues compared to that in adjacent normal tissues. All these results suggested that PHA-E-positive Cp could be a potential PC-specific glycoprotein marker to distinguish PC patients from acute pancreatitis patients and normal persons.
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Prinz C, Fehring L, Frese R. MicroRNAs as Indicators of Malignancy in Pancreatic Ductal Adenocarcinoma (PDAC) and Cystic Pancreatic Lesions. Cells 2022; 11:cells11152374. [PMID: 35954223 PMCID: PMC9368175 DOI: 10.3390/cells11152374] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 07/25/2022] [Accepted: 07/30/2022] [Indexed: 12/04/2022] Open
Abstract
The dysregulation of microRNAs has recently been associated with cancer development and progression in pancreatic ductal adenocarcinoma (PDAC) and cystic pancreatic lesions. In solid pancreatic tumor tissue, the dysregulation of miR-146, miR-196a/b, miR-198, miR-217, miR-409, and miR-490, as well as miR-1290 has been investigated in tumor biopsies of patients with PDAC and was reported to predict cancer presence. However, the value of the predictive biomarkers may further be increased during clinical conditions suggesting cancer development such as hyperinsulinemia or onset of diabetes. In this specific context, the dysregulation of miR-486 and miR-196 in tumors has been observed in the tumor tissue of PDAC patients with newly diagnosed diabetes mellitus. Moreover, miR-1256 is dysregulated in pancreatic cancer, possibly due to the interaction with long non-coding RNA molecules that seem to affect cell-cycle control and diabetes manifestation in PDAC patients, and, thus, these three markers may be of special or “sentinel value”. In blood samples, Next-generation sequencing (NGS) has also identified a set of microRNAs (miR-20a, miR-31-5p, miR-24, miR-25, miR-99a, miR-185, and miR-191) that seem to differentiate patients with pancreatic cancer remarkably from healthy controls, but limited data exist in this context regarding the prediction of cancer presences and outcomes. In contrast to solid pancreatic tumors, in cystic pancreatic cancer lesions, as well as premalignant lesions (such as intraductal papillary neoplasia (IPMN) or mucinous-cystic adenomatous cysts (MCAC)), the dysregulation of a completely different expression panel of miR-31-5p, miR-483-5p, miR-99a-5p, and miR-375 has been found to be of high clinical value in differentiating benign from malignant lesions. Interestingly, signal transduction pathways associated with miR-dysregulation seem to be entirely different in patients with pancreatic cysts when compared to PDAC. Overall, the determination of these different dysregulation “panels” in solid tumors, pancreatic cysts, obtained via fine-needle aspirate biopsies and/or in blood samples at the onset or during the treatment of pancreatic diseases, seems to be a reasonable candidate approach for predicting cancer presence, cancer development, and even therapy responses.
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Soheilifar MH, Pornour M, Saidijam M, Najafi R, Azizi Jalilian F, Keshmiri Neghab H, Amini R. miR-1290 contributes to oncogenesis and angiogenesis via targeting of THBS1, DKK3 and, SCAI. BIOIMPACTS 2022; 12:349-358. [PMID: 35975203 PMCID: PMC9376166 DOI: 10.34172/bi.2021.23571] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 03/22/2021] [Accepted: 04/27/2021] [Indexed: 11/09/2022]
Abstract
Introduction: Colorectal cancer (CRC) is the third most common cancer in the world with high mortality, hence, understanding the molecular mechanisms involved in the tumor progression are important for CRC diagnosis and treatment. MicroRNAs (miRNAs) are key gene expression regulators that can function as tumor suppressors or oncogenes in tumor cells, and modulate angiogenesis as a critical process in tumor metastasis. MiR-1290 has been demonstrated as an onco-miRNA in various types of cancer, however, the role of miR-1290 in CRC is not fully understood. This study aimed to investigate the oncogenic and angiogenic potential of miR-1290 in CRC. Methods: Lenti-miR-1290 was transduced into HCT116, SW480, and human umbilical vein endothelial cells (HUVECs). By bioinformatics analysis, we identified thrombospondin 1 (THBS1) as a novel predicted target for miR-1290. Quantitative real-time PCR, western blotting, and luciferase reporter assay were used to demonstrate suppression of miR-1290 target genes including THBS1, Dickkopf Wnt signaling pathway inhibitor 3 (DKK3), and suppressor of cancer cell invasion (SCAI) in HCT116 and HUVECs. Cell cycle analysis, proliferation, migration and, tube formation were determined by flow cytometry, MTT, wound healing, and tube formation assays, respectively. Results: MiR-1290 significantly decreased the expression of THBS1, DKK3, and SCAI. We demonstrated that miR-1290 enhanced proliferation, migration, and angiogenesis partially through suppression of THBS1, DKK3, and SCAI in CRC. Conclusion: These results suggest a novel function of miR-1290 which may contribute to tumorigenesis and angiogenesis in CRC.
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Affiliation(s)
- Mohammad Hasan Soheilifar
- Research Center for Molecular Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, 6517838678, Iran
| | - Majid Pornour
- Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECR, Tehran, 1315795613, Iran
| | - Massoud Saidijam
- Research Center for Molecular Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, 6517838678, Iran
| | - Rezvan Najafi
- Research Center for Molecular Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, 6517838678, Iran
| | - Farid Azizi Jalilian
- Department of Virology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, 6517838678, Iran
| | - Hoda Keshmiri Neghab
- Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECR, Tehran, 1315795613, Iran
| | - Razieh Amini
- Research Center for Molecular Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, 6517838678, Iran
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Ohtsubo K, Miyake K, Arai S, Fukuda K, Suzuki C, Kotani H, Tanimoto A, Nishiyama A, Nanjo S, Yamashita K, Takeuchi S, Yano S. Methylation of Tumor Suppressive miRNAs in Plasma from Patients With Pancreaticobiliary Diseases. CANCER DIAGNOSIS & PROGNOSIS 2022; 2:378-383. [PMID: 35530650 PMCID: PMC9066530 DOI: 10.21873/cdp.10120] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 03/04/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND/AIM We previously reported the usefulness of aberrant methylation of tumor suppressive miRNAs in bile to discriminate pancreaticobiliary cancers (PBCs) from benign pancreaticobiliary diseases (BD). Here we performed a methylation analysis of plasma miRNAs to identify miRNAs specific for PBCs. PATIENTS AND METHODS Plasma was collected from 80 patients with pancreatic cancer (PC); 18 with biliary tract cancer (BTC) and 28 with BD. Sequences encoding 3 tumor suppressive miRNAs (miR-200a, -200b, and -1247) were PCR amplified and sequenced, and their methylation rates were determined. RESULTS The methylation rate of miR-1247 was significantly higher in patients with BTC than in those with BD, and tended to be higher in patients with PC than in those with BD. Furthermore, it was significantly higher in three patients with stages I/II BTC than in those with BD. CONCLUSION Methylation of miR-1247 in plasma may be useful to distinguish BTC from BD.
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Affiliation(s)
- Koushiro Ohtsubo
- Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Kunio Miyake
- Department of Health Sciences, School of Medicine, University of Yamanashi, Chuo, Japan
| | - Sachiko Arai
- Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Koji Fukuda
- Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Chiaki Suzuki
- Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Hiroshi Kotani
- Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Azusa Tanimoto
- Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Akihiro Nishiyama
- Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Shigeki Nanjo
- Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Kaname Yamashita
- Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Shinji Takeuchi
- Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Seiji Yano
- Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
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miR-1290 modulates the radioresistance of triple-negative breast cancer by targeting NLRP3-mediated pyroptosis. Clin Transl Oncol 2022; 24:1764-1775. [PMID: 35471684 DOI: 10.1007/s12094-022-02831-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 03/30/2022] [Indexed: 12/19/2022]
Abstract
PURPOSE To explore the roles and underlying mechanisms of miR-1290 in determining the sensitivity of triple-negative breast cancer (TNBC) to radiation therapy. METHODS ELISA was performed to detect the levels of IL-18 and IL-1β in radiosensitive cells and serum samples. The level of miR-1290 in radiosensitive cells and tissues was assessed by qRT-PCR assay. A luciferase reporter assay was performed to confirm NLRP3 as the target of miR-1290. Functionally, the roles of miR-1290 in TNBC radioresistance were analyzed by transfection of either miR-1290 mimic or miR-1290 inhibitor. Moreover, the involvement of the miR-1290/NLRP3 axis in TNBC radioresistance was analyzed by experiments with a miR-1290 mimic and NLRP3 overexpression. MTT and colony formation assays were used to detect radiation-induced cell viability and proliferation. qRT-PCR and western blot assays were used to detect pyroptosis markers (NLRP3, ACS and caspase-1). RESULTS The results showed that radioresistance in TNBC cells was associated with a reduction in pyroptosis. miR-1290 expression was increased in radioresistant cells, and it had higher expression levels in the radioresistant tumor tissues of TNBC patients compared to the radiosensitive samples. The miR-1290 mimic suppressed radiation-induced pyroptosis and reduced the radiosensitivity of TNBC cells. Moreover, we found that NLRP3 was a potential target of miR-1290. Overexpression of NLRP3 partly reversed the effects of miR-1290 on pyroptosis and radioresistance. The mouse models showed that miR-1290 suppressed tumor size, tumor weight and pyroptosis. CONCLUSIONS miR-1290/NLRP3-mediated pyroptosis may play an important role in determining radioresistance in TNBC and serve as a novel therapeutic option.
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Permuth JB, Mesa T, Williams SL, Cardentey Y, Zhang D, Pawlak EA, Li J, Cameron ME, Ali KN, Jeong D, Yoder SJ, Chen DT, Trevino JG, Merchant N, Malafa M. A pilot study to troubleshoot quality control metrics when assessing circulating miRNA expression data reproducibility across study sites. Cancer Biomark 2022; 33:467-478. [PMID: 35491771 PMCID: PMC9428925 DOI: 10.3233/cbm-210255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND: Given the growing interest in using microRNAs (miRNAs) as biomarkers of early disease, establishment of robust protocols and platforms for miRNA quantification in biological fluids is critical. OBJECTIVE: The goal of this multi-center pilot study was to evaluate the reproducibility of NanoString nCounter™ technology when analyzing the abundance of miRNAs in plasma and cystic fluid from patients with pancreatic lesions. METHODS: Using sample triplicates analyzed across three study sites, we assessed potential sources of variability (RNA isolation, sample processing/ligation, hybridization, and lot-to-lot variability) that may contribute to suboptimal reproducibility of miRNA abundance when using nCounter™, and evaluated expression of positive and negative controls, housekeeping genes, spike-in genes, and miRNAs. RESULTS: Positive controls showed a high correlation across samples from each site (median correlation coefficient, r> 0.9). Most negative control probes had expression levels below background. Housekeeping and spike-in genes each showed a similar distribution of expression and comparable pairwise correlation coefficients of replicate samples across sites. A total of 804 miRNAs showed a similar distribution of pairwise correlation coefficients between replicate samples (p= 0.93). After normalization and selecting miRNAs with expression levels above zero in 80% of samples, 55 miRNAs were identified; heatmap and principal component analysis revealed similar expression patterns and clustering in replicate samples. CONCLUSIONS: Findings from this pilot investigation suggest the nCounter platform can yield reproducible results across study sites. This study underscores the importance of implementing quality control procedures when designing multi-center evaluations of miRNA abundance.
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Affiliation(s)
- Jennifer B. Permuth
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Tania Mesa
- Molecular Genomics Core Facility, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Sion L. Williams
- Oncogenomics Shared Resource, Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Yoslayma Cardentey
- Oncogenomics Shared Resource, Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Dongyu Zhang
- Department of Cancer Epidemiology, University of Florida, Gainesville, FL, USA
| | | | - Jiannong Li
- Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Miles E. Cameron
- College of Medicine, University of Florida, Gainesville, FL, USA
| | - Karla N. Ali
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Daniel Jeong
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
- Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Tampa, FL, USA
| | - Sean J. Yoder
- Molecular Genomics Core Facility, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Dung-Tsa Chen
- Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Jose G. Trevino
- Department of Surgery, University of Florida, Gainesville, FL, USA
- Department of Surgery, Division of Surgical Oncology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Nipun Merchant
- Department of Surgery, Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Mokenge Malafa
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
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Jia YZ, Liu J, Wang GQ, Song ZF. miR-484: A Potential Biomarker in Health and Disease. Front Oncol 2022; 12:830420. [PMID: 35356223 PMCID: PMC8959652 DOI: 10.3389/fonc.2022.830420] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 02/11/2022] [Indexed: 01/30/2023] Open
Abstract
Disorders of miR-484 expression are observed in cancer, different diseases or pathological states. There is accumulating evidence that miR-484 plays an essential role in the development as well as the regression of different diseases, and miR-484 has been reported as a key regulator of common cancer and non-cancer diseases. The miR-484 targets that have effects on inflammation, apoptosis and mitochondrial function include SMAD7, Fis1, YAP1 and BCL2L13. For cancer, identified targets include VEGFB, VEGFR2, MAP2, MMP14, HNF1A, TUSC5 and KLF12. The effects of miR-484 on these targets have been documented separately. Moreover, miR-484 is typically described as an oncosuppressor, but this claim is simplistic and one-sided. This review will combine relevant basic and clinical studies to find that miR-484 promotes tumorigenesis and metastasis in liver, prostate and lung tissues. It will provide a basis for the possible mechanisms of miR-484 in early tumor diagnosis, prognosis determination, disease assessment, and as a potential therapeutic target for tumors.
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Affiliation(s)
- Yin-Zhao Jia
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Liu
- Key Laboratory of Coal Science and Technology of Ministry of Education, College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan, China
| | - Geng-Qiao Wang
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zi-Fang Song
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Pancreatic Neuroendocrine Neoplasms: Updates on Genomic Changes in Inherited Tumour Syndromes and Sporadic Tumours Based on WHO Classification. Crit Rev Oncol Hematol 2022; 172:103648. [PMID: 35248713 DOI: 10.1016/j.critrevonc.2022.103648] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 02/19/2022] [Accepted: 02/28/2022] [Indexed: 12/16/2022] Open
Abstract
Pancreatic neuroendocrine neoplasms (PanNENs) are the neuroendocrine neoplasms with greatest rate of increase in incidence. Approximately 10% of PanNENs arise as inherited tumour syndromes which include multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 4, von Hippel-Lindau syndrome, neurofibromatosis type1, tuberous sclerosis complex 1/2, Cowden syndrome, and Glucagon cell hyperplasia and neoplasia as well as familial insulinomatosis. In sporadic PanNENs, driver mutations in MEN1, DAXX/ATRX and mTOR pathway genes are associated with development and progression in pancreatic neuroendocrine tumours. The other changes are in VEGF pathway, Notch pathway, germline mutations in MUTYH, CHEK2, BRCA2, PHLDA3 as well as other genetic alterations. On the other hand, pancreatic neuroendocrine carcinomas share similar genetic alterations with ductal adenocarcinomas, e.g., TP53, RB1 or KRAS. In addition, microRNA and changes in immune microenvironment were noted in PanNENs. Updates on these genetic knowledges contribute to the development of management strategies for patients with PanNENs.
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Prisciandaro M, Antista M, Raimondi A, Corti F, Morano F, Centonze G, Sabella G, Mangogna A, Randon G, Pagani F, Prinzi N, Niger M, Corallo S, Castiglioni di Caronno E, Massafra M, Bartolomeo MD, de Braud F, Milione M, Pusceddu S. Biomarker Landscape in Neuroendocrine Tumors With High-Grade Features: Current Knowledge and Future Perspective. Front Oncol 2022; 12:780716. [PMID: 35186729 PMCID: PMC8856722 DOI: 10.3389/fonc.2022.780716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 01/10/2022] [Indexed: 11/26/2022] Open
Abstract
Neuroendocrine tumors (NETs) are classified based on morphology and are graded based on their proliferation rate as either well-differentiated low-grade (G1) to intermediate (G2–G3) or poorly differentiated high-grade neuroendocrine carcinomas (NEC G3). Recently, in gastroenteropancreatic (GEP) NETs, a new subgroup of well-differentiated high-grade tumors (NET G3) has been divided from NEC by WHO due to its different clinical–pathologic features. Although several mutational analyses have been performed, a molecular classification of NET is an unmet need in particular for G3, which tends to be more aggressive and have less benefit to the available therapies. Specifically, new possible prognostic and, above all, predictive factors are highly awaited, giving the basis for new treatments. Alteration of KRAS, TP53, and RB1 is mainly reported, but also druggable alterations, including BRAF and high microsatellite instability (MSI-H), have been documented in subsets of patients. In addition, PD-L1 demonstrated to be highly expressed in G3 NETs, probably becoming a new biomarker for G3 neuroendocrine neoplasm (NEN) discrimination and a predictive one for immunotherapy response. In this review, we describe the current knowledge available on a high-grade NET molecular landscape with a specific focus on those harboring potentially therapeutic targets in the advanced setting.
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Affiliation(s)
- Michele Prisciandaro
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
- *Correspondence: Michele Prisciandaro,
| | - Maria Antista
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Alessandra Raimondi
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Francesca Corti
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Federica Morano
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanni Centonze
- First Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanna Sabella
- First Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Alessandro Mangogna
- Institute for Maternal and Child Health, IRCCS Burlo Garofalo, Trieste, Italy
| | - Giovanni Randon
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Filippo Pagani
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Natalie Prinzi
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Monica Niger
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Salvatore Corallo
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | | | - Marco Massafra
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Maria Di Bartolomeo
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Filippo de Braud
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Massimo Milione
- First Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Sara Pusceddu
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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Guz M, Jeleniewicz W, Cybulski M. An Insight into miR-1290: An Oncogenic miRNA with Diagnostic Potential. Int J Mol Sci 2022; 23:1234. [PMID: 35163157 PMCID: PMC8835968 DOI: 10.3390/ijms23031234] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/11/2022] [Accepted: 01/19/2022] [Indexed: 12/12/2022] Open
Abstract
For more than two decades, the view of the roles of non-coding RNAs (ncRNAs) has been radically changing. These RNA molecules that are transcribed from our genome do not have the capacity to encode proteins, but are critical regulators of gene expression at different levels. Our knowledge is constantly enriched by new reports revealing the role of these new molecular players in the development of many pathological conditions, including cancer. One of the ncRNA classes includes short RNA molecules called microRNAs (miRNAs), which are involved in the post-transcriptional control of gene expression affecting various cellular processes. The aberrant expression of miRNAs with oncogenic and tumor-suppressive function is associated with cancer initiation, promotion, malignant transformation, progression and metastasis. Oncogenic miRNAs, also known as oncomirs, mediate the downregulation of tumor-suppressor genes and their expression is upregulated in cancer. Nowadays, miRNAs show promising application in diagnosis, prediction, disease monitoring and therapy response. Our review presents a current view of the oncogenic role of miR-1290 with emphasis on its properties as a cancer biomarker in clinical medicine.
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Affiliation(s)
- Małgorzata Guz
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland; (W.J.); (M.C.)
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Ghafouri-Fard S, Khoshbakht T, Hussen BM, Taheri M, Samadian M. A Review on the Role of miR-1290 in Cell Proliferation, Apoptosis and Invasion. Front Mol Biosci 2022; 8:763338. [PMID: 35004844 PMCID: PMC8740132 DOI: 10.3389/fmolb.2021.763338] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 11/24/2021] [Indexed: 11/13/2022] Open
Abstract
MicroRNAs (miRNAs) have been shown to affect expression of several genes contributing in important biological processes. miR-1290 a member of this family with crucial roles in the carcinogenesis. This miRNA is transcribed from MIR1290 gene on chromosome 1p36.13. This miRNA has interactions with a number of mRNA coding genes as well as non-coding RNAs SOCS4, GSK3, BCL2, CCNG2, KIF13B, INPP4B, hMSH2, KIF13B, NKD1, FOXA1, IGFBP3, CCAT1, FOXA1, NAT1, SMEK1, SCAI, ZNF667-AS1, ABLIM1, Circ_0000629 and CDC73. miR-1290 can also regulate activity of JAK/STAT3, PI3K/AKT, Wnt/β-catenin and NF-κB molecular pathways. Most evidence indicates the oncogenic roles of miR-1290, yet controversial evidence also exists. In the present review, we describe the results of in vitro, animal and human investigations about the impact of miR-1290 in the development of malignancies.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tayyebeh Khoshbakht
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Kurdistan Region, Iraq
| | - Mohammad Taheri
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Institute of Human Genetics, Jena University Hospital, Jena, Germany
| | - Mohammad Samadian
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Circulating Exosomal miR-1290 for Diagnosis of Epithelial Ovarian Cancer. Curr Issues Mol Biol 2022; 44:288-300. [PMID: 35723400 PMCID: PMC8928998 DOI: 10.3390/cimb44010021] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 01/04/2022] [Accepted: 01/07/2022] [Indexed: 12/25/2022] Open
Abstract
The aim of the study was to develop a new diagnostic biomarker for identifying serum exosomal miRNAs specific to epithelial ovarian cancer (EOC) and to find out target gene of the miRNA for exploring the molecular mechanisms in EOC. A total of 84 cases of ovarian masses and sera were enrolled, comprising EOC (n = 71), benign ovarian neoplasms (n = 13). We detected expression of candidate miRNAs in the serum and tissue of both benign ovarian neoplasm group and EOC group using real-time polymerase chain reaction. Immunohistochemistry were constructed using formalin fixed paraffin embedded (FFPE) tissue to detect expression level of suppressor of cytokine signaling 4 (SOCS4). In the EOC group, miRNA-1290 was significantly overexpressed in serum exosomes and tissues as compared to benign ovarian neoplasm group (fold change ≥ 2, p < 0.05). We observed area under the receiver operating characteristic curve (AUC) for miR-1290, using a cut-off of 0.73, the exosomal miR-1290 from serum had AUC, sensitivity, and specificity values of 0.794, 69.2 and 87.3, respectively. In immunohistochemical study, expression of SOCS4 in EOC was lower than that in benign ovarian neoplasm. Serum exosomal miR-1290 could be considered as a biomarker for differential diagnosis of EOC from benign ovarian neoplasm and SOCS4 might be potential target gene of miR-1290 in EOC.
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Kalhori MR, Soleimani M, Arefian E, Alizadeh AM, Mansouri K, Echeverria J. The potential role of miR-1290 in cancer progression, diagnosis, prognosis, and treatment: An oncomiR or onco-suppressor microRNA? J Cell Biochem 2021; 123:506-531. [PMID: 34897783 DOI: 10.1002/jcb.30191] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 07/20/2021] [Accepted: 11/24/2021] [Indexed: 12/11/2022]
Abstract
Cancer is one of the leading causes of death in humans because of the lack of early diagnosis, distant metastases, and the resistance to adjuvant therapies, including chemotherapy and radiotherapy. In addition to playing an essential role in tumor progression and development, microRNAs (miRNAs) can be used as a robust biomarker in the early detection of cancer. MiR-1290 was discovered for the first time in human embryonic stem cells, and under typical physiological situations, plays an essential role in neuronal differentiation and neural stem cell proliferation. Its coding sequence is located at the 1p36.13 regions in the first intron of the aldehyde dehydrogenase 4 gene member A1. miR-1290 is out of control in many cancers such as breast cancer, colorectal cancer, esophageal squamous cell carcinoma, gastric cancer, lung cancer, pancreatic cancer, and plays a vital role in their development. Therefore, it is suggested that miR-1290 can be considered as a potential diagnostic and therapeutic target in many cancers. In addition to the importance of miR-1290 in the noninvasive diagnosis of various cancers, this systematic review study discussed the role of miR-1290 in altering the expression of different genes involved in cancer development and chemo-radiation resistance. Moreover, it considered the regulatory effect of natural products on miR-1290 expression and the interaction of lncRNAs by miR-1290.
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Affiliation(s)
- Mohammad Reza Kalhori
- Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Masoud Soleimani
- Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ehsan Arefian
- Department of Microbiology, Molecular Virology Lab, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Ali Mohammad Alizadeh
- Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Kamran Mansouri
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Javier Echeverria
- Departamento de Ciencias del Ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile
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Sung MK, Park Y, Kwak BJ, Jun E, Lee W, Song KB, Lee JH, Hwang DW, Kim SC. Comparison of Characteristics and Survival Rates of Resectable Pancreatic Ductal Adenocarcinoma according to Tumor Location. Biomedicines 2021; 9:1706. [PMID: 34829935 PMCID: PMC8615679 DOI: 10.3390/biomedicines9111706] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/11/2021] [Accepted: 11/14/2021] [Indexed: 12/25/2022] Open
Abstract
The impact of tumor location on patient survival in pancreatic ductal adenocarcinoma (PDAC) remains controversial. This study investigated the association between primary tumor location and survival rates for resectable PDAC. Additionally, we assessed if this association remains consistent across categories of the Tumor-Node-Metastasis staging system. We analyzed 2471 patients who underwent surgical resection between 2000 and 2018 at a single center. Subgroup analysis was performed according to the Tumor-Node-Metastasis staging system. Among the group, 67.9% (1677 patients) had pancreatic head cancer (PHC) and 32.1% (794 patients) had pancreatic body/tail cancer (PBTC). Patients with PHC had worse overall survival and worse disease-free survival than those with PBTC. Patients with PHC had worse survival in stage IB and stage IIB than those with PBTC. No significant difference was observed for stages IA, IIA, and III. Multivariate analysis showed that elevated CA 19-9, mGPS, a longer hospital stay, complication, accompanying vein resection, larger tumor size, worse differentiation, higher TNM stage (stage IIB, III, IV), presence of LVI, and positive resection margin were risk factors for poor survival after resection. In resectable PDAC, patients with PHC had worse overall and disease-free survival than those with PBTC. However, tumor location was not an independent prognostic factor for PDAC.
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Affiliation(s)
- Min Kyu Sung
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Korea; (M.K.S.); (Y.P.); (B.J.K.); (E.J.); (W.L.); (K.B.S.); (J.H.L.); (D.W.H.)
| | - Yejong Park
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Korea; (M.K.S.); (Y.P.); (B.J.K.); (E.J.); (W.L.); (K.B.S.); (J.H.L.); (D.W.H.)
| | - Bong Jun Kwak
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Korea; (M.K.S.); (Y.P.); (B.J.K.); (E.J.); (W.L.); (K.B.S.); (J.H.L.); (D.W.H.)
| | - Eunsung Jun
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Korea; (M.K.S.); (Y.P.); (B.J.K.); (E.J.); (W.L.); (K.B.S.); (J.H.L.); (D.W.H.)
- Convergence Medicine, University of Ulsan College of Medicine, Seoul 05505, Korea
| | - Woohyung Lee
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Korea; (M.K.S.); (Y.P.); (B.J.K.); (E.J.); (W.L.); (K.B.S.); (J.H.L.); (D.W.H.)
| | - Ki Byung Song
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Korea; (M.K.S.); (Y.P.); (B.J.K.); (E.J.); (W.L.); (K.B.S.); (J.H.L.); (D.W.H.)
| | - Jae Hoon Lee
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Korea; (M.K.S.); (Y.P.); (B.J.K.); (E.J.); (W.L.); (K.B.S.); (J.H.L.); (D.W.H.)
| | - Dae Wook Hwang
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Korea; (M.K.S.); (Y.P.); (B.J.K.); (E.J.); (W.L.); (K.B.S.); (J.H.L.); (D.W.H.)
| | - Song Cheol Kim
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Korea; (M.K.S.); (Y.P.); (B.J.K.); (E.J.); (W.L.); (K.B.S.); (J.H.L.); (D.W.H.)
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Schlick K, Kiem D, Greil R. Recent Advances in Pancreatic Cancer: Novel Prognostic Biomarkers and Targeted Therapy-A Review of the Literature. Biomolecules 2021; 11:1469. [PMID: 34680101 PMCID: PMC8533343 DOI: 10.3390/biom11101469] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 09/27/2021] [Accepted: 10/01/2021] [Indexed: 12/14/2022] Open
Abstract
Pancreatic adenocarcinoma carries a devastating prognosis. For locally advanced and metastatic disease, several chemotherapeutic regimens are currently being used. Over the past years, novel approaches have included targeting EGFR, NTRK, PARP, K-Ras as well as stroma and fibrosis, leading to approval of NTRK and PARP inhibitors. Moreover, immune check point inhibitors and different combinational approaches involving immunotherapeutic agents are being investigated in many clinical trials. MiRNAs represent a novel tool and are thought to greatly improve management by allowing for earlier diagnosis and for more precise guidance of treatment.
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Affiliation(s)
- Konstantin Schlick
- Oncologic Center, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Paracelsus Medical University, 5020 Salzburg, Austria; (K.S.); (D.K.)
- Cancer Cluster Salzburg, 5020 Salzburg, Austria
| | - Dominik Kiem
- Oncologic Center, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Paracelsus Medical University, 5020 Salzburg, Austria; (K.S.); (D.K.)
- Cancer Cluster Salzburg, 5020 Salzburg, Austria
| | - Richard Greil
- Oncologic Center, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Paracelsus Medical University, 5020 Salzburg, Austria; (K.S.); (D.K.)
- Cancer Cluster Salzburg, 5020 Salzburg, Austria
- Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Salzburg Cancer Research Institute, 5020 Salzburg, Austria
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Pancreatic Cancer Small Extracellular Vesicles (Exosomes): A Tale of Short- and Long-Distance Communication. Cancers (Basel) 2021; 13:cancers13194844. [PMID: 34638330 PMCID: PMC8508300 DOI: 10.3390/cancers13194844] [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: 08/30/2021] [Revised: 09/21/2021] [Accepted: 09/24/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Even today, pancreatic cancer still has a dismal prognosis. It is characterized by a lack of early symptoms and thus late diagnosis as well as early metastasis. The majority of patients suffer from pancreatic ductal adenocarcinoma (PDAC). PDACs communicate extensively with cellular components of their microenvironment, but also with distant metastatic niches to facilitate tumor progression and dissemination. This crosstalk is substantially enabled by small extracellular vesicles (sEVs, exosomes) with a size of 30–150 nm that are released from the tumor cells. sEVs carry bioactive cargos that reprogram target cells to promote tumor growth, migration, metastasis, immune evasion, or chemotherapy resistance. Interestingly, sEVs also carry novel diagnostic, prognostic and potentially also predictive biomarkers. Moreover, engineered sEVs may be utilized as therapeutic agents, improving treatment options. The role of sEVs for PDAC development, progression, diagnosis, prognosis, and treatment is the focus of this review. Abstract Even with all recent advances in cancer therapy, pancreatic cancer still has a dismal 5-year survival rate of less than 7%. The most prevalent tumor subtype is pancreatic ductal adenocarcinoma (PDAC). PDACs display an extensive crosstalk with their tumor microenvironment (TME), e.g., pancreatic stellate cells, but also immune cells to regulate tumor growth, immune evasion, and metastasis. In addition to crosstalk in the local TME, PDACs were shown to induce the formation of pre-metastatic niches in different organs. Recent advances have attributed many of these interactions to intercellular communication by small extracellular vesicles (sEVs, exosomes). These nanovesicles are derived of endo-lysosomal structures (multivesicular bodies) with a size range of 30–150 nm. sEVs carry various bioactive cargos, such as proteins, lipids, DNA, mRNA, or miRNAs and act in an autocrine or paracrine fashion to educate recipient cells. In addition to tumor formation, progression, and metastasis, sEVs were described as potent biomarker platforms for diagnosis and prognosis of PDAC. Advances in sEV engineering have further indicated that sEVs might once be used as effective drug carriers. Thus, extensive sEV-based communication and applications as platform for biomarker analysis or vehicles for treatment suggest a major impact of sEVs in future PDAC research.
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Smolarz B, Durczyński A, Romanowicz H, Hogendorf P. The Role of microRNA in Pancreatic Cancer. Biomedicines 2021; 9:biomedicines9101322. [PMID: 34680441 PMCID: PMC8533140 DOI: 10.3390/biomedicines9101322] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 09/18/2021] [Accepted: 09/22/2021] [Indexed: 12/12/2022] Open
Abstract
MicroRNAs (miRNAs) are small ribonucleic acid molecules that play a key role in regulating gene expression. The increasing number of studies undertaken on the functioning of microRNAs in the tumor formation clearly indicates their important potential in oncological therapy. Pancreatic cancer is one of the deadliest cancers. The expression of miRNAs released into the bloodstream appears to be a good indicator of progression and evaluation of the aggressiveness of pancreatic cancer, as indicated by studies. The work reviewed the latest literature on the importance of miRNAs for pancreatic cancer development.
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Affiliation(s)
- Beata Smolarz
- Laboratory of Cancer Genetics, Department of Pathology, Polish Mother’s Memorial Hospital Research Institute, 93-338 Lodz, Poland;
- Correspondence: ; Tel.: +48-42-271-1290
| | - Adam Durczyński
- Department of General and Transplant Surgery, N. Barlicki Memorial Clinical Hospital, Medical University of Lodz, 90-153 Lodz, Poland; (A.D.); (P.H.)
| | - Hanna Romanowicz
- Laboratory of Cancer Genetics, Department of Pathology, Polish Mother’s Memorial Hospital Research Institute, 93-338 Lodz, Poland;
| | - Piotr Hogendorf
- Department of General and Transplant Surgery, N. Barlicki Memorial Clinical Hospital, Medical University of Lodz, 90-153 Lodz, Poland; (A.D.); (P.H.)
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Xu L, Cai Y, Chen X, Zhu Y, Cai J. Circulating MiR-1290 as a potential diagnostic and disease monitoring biomarker of human gastrointestinal tumors. BMC Cancer 2021; 21:989. [PMID: 34479528 PMCID: PMC8417985 DOI: 10.1186/s12885-021-08729-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 08/26/2021] [Indexed: 12/14/2022] Open
Abstract
Background Gastrointestinal tumors are a leading cause of mortality worldwide. As shown in our previous study, miR-1290 is overexpressed in colorectal cancer (CRC) and promotes tumor progression. We therefore aimed to explore the potential of circulating miR-1290 as a biomarker for gastrointestinal cancer. Methods A serum miRNA sequencing analysis was performed. Then, circulating miRNA detection technologies were established. The expression of miR-1290 was analyzed in gastrointestinal tumor cell lines and culture supernatants. Expression levels of circulating miR-1290 in clinical samples were examined. Associations between miR-1290 expression and clinicopathologic characteristics were analyzed. Xenograft models were generated to assess the fluctuation in serum miR-1290 levels during disease progression. Results Through miRNA sequencing, we identified that miR-1290 was overexpressed in serum samples from patients with CRC. We confirmed that human gastrointestinal tumor cells express and secrete miR-1290. The circulating miR-1290 levels was up-regulated in patients with pancreatic cancer (PC) (p < 0.01), CRC (p < 0.05), and gastric cancer (GC) (p < 0.01). High miR-1290 expression levels were associated with tumor size, lymphatic invasion, vascular invasion, distant metastasis, tumor differentiation and AJCC stage in patients with PC and CRC. The area under the curve (AUC) was 0.8857 in patients with PC, with 60.9% sensitivity and 90.0% specificity. The AUC was 0.7852 in patients with CRC, with 42.0% sensitivity and 90.0% specificity. In patients with GC, the AUC was 0.6576, with 26.0% sensitivity and 90.0% specificity. The in vivo model verified that the circulating miR-1290 level was significantly increased after tumor formation and decreased after drug treatment. Conclusions Our findings indicate that circulating miR-1290 is a potential biomarker for gastrointestinal cancer diagnosis and monitoring. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08729-0.
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Affiliation(s)
- Liyi Xu
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, Province, China
| | - Yangke Cai
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, Province, China
| | - Xiao Chen
- Emergency Department, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Yongliang Zhu
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, Province, China.
| | - Jianting Cai
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, Province, China.
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The Role of miRNA in the Pathophysiology of Neuroendocrine Tumors. Int J Mol Sci 2021; 22:ijms22168569. [PMID: 34445276 PMCID: PMC8395312 DOI: 10.3390/ijms22168569] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/16/2021] [Accepted: 08/06/2021] [Indexed: 12/14/2022] Open
Abstract
Neuroendocrine tumors (NETs) represent a tumor group that is both rare and heterogeneous. Prognosis is largely determined by the tumor grading and the site of the primary tumor and metastases. Despite intensive research efforts, only modest advances in diagnostic and therapeutic approaches have been achieved in recent years. For patients with non-respectable tumor stages, prognosis is poor. In this context, the development of novel diagnostic tools for early detection of NETs and prediction of tumor response to therapy as well as estimation of the overall prognosis would greatly improve the clinical management of NETs. However, identification of novel diagnostic molecules is hampered by an inadequate understanding of the pathophysiology of neuroendocrine malignancies. It has recently been demonstrated that microRNA (miRNA), a family of small RNA molecules with an established role in the pathophysiology of quite different cancer entities, may also play a role as a biomarker. Here, we summarize the available knowledge on the role of miRNAs in the development of NET and highlight their potential use as serum-based biomarkers in the context of this disease. We discuss important challenges currently preventing their use in clinical routine and give an outlook on future directions of miRNA research in NET.
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50
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Yang J, Xu R, Wang C, Qiu J, Ren B, You L. Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review. Cancer Commun (Lond) 2021; 41:1257-1274. [PMID: 34331845 PMCID: PMC8696234 DOI: 10.1002/cac2.12204] [Citation(s) in RCA: 158] [Impact Index Per Article: 39.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 06/15/2021] [Accepted: 07/26/2021] [Indexed: 12/14/2022] Open
Abstract
Pancreatic cancer is a highly malignant digestive system tumor with a poor prognosis. Most pancreatic cancer patients are diagnosed at an advanced stage or even metastasis due to its highly aggressive characteristics and lack of typical early symptoms. Thus, an early diagnosis of pancreatic cancer is crucial for improving its prognosis. Currently, screening is often applied in high‐risk individuals to achieve the early diagnosis of pancreatic cancer. Fully understanding the risk factors of pancreatic cancer and pathogenesis could help us identify the high‐risk population and achieve early diagnosis and timely treatment of pancreatic cancer. Notably, accumulating studies have been undertaken to improve the detection rate of different imaging methods and the diagnostic accuracy of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) which is the golden standard for pancreatic cancer diagnosis. In addition, there are currently no biomarkers with sufficient sensitivity and specificity for the diagnosis of pancreatic cancer to be applied in the clinic. As the only serum biomarker approved by the United States Food and Drug Administration, carbohydrate antigen 19‐9 (CA19‐9) is not recommended to be used in the early screening of pancreatic cancer because of its limited specificity. Recently, increasing numbers of studies focused on the discovering of novel serum biomarkers and exploring their combination with CA19‐9 in the detection of pancreatic cancer. Besides, the application of liquid biopsy involving circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNAs (miRNAs), and exosomes in blood and biomarkers in urine, and saliva in pancreatic cancer diagnosis are drawing more and more attention. Furthermore, many innovative technologies such as artificial intelligence, computer‐aided diagnosis system, metabolomics technology, ion mobility spectrometry (IMS) associated technologies, and novel nanomaterials have been tested for the early diagnosis of pancreatic cancer and have shown promising prospects. Hence, this review aims to summarize the recent progress in the development of early screening and diagnostic methods, including imaging, pathological examination, serological examination, liquid biopsy, as well as other potential diagnostic strategies for pancreatic cancer.
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Affiliation(s)
- Jinshou Yang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, P. R. China
| | - Ruiyuan Xu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, P. R. China
| | - Chengcheng Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, P. R. China
| | - Jiangdong Qiu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, P. R. China
| | - Bo Ren
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, P. R. China
| | - Lei You
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, P. R. China
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