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Guney Eskiler G, Karabay O, Tozlu M, Aydin A, Hamarat KF, Alkurt U, Deveci Ozkan A, Gunduz Y. The Predictive Role of miRNAs in Hepatitis B Vaccine Response of Metabolic Dysfunction-Associated Steatotic Liver Disease Patients. Viruses 2024; 16:1799. [PMID: 39599914 PMCID: PMC11598886 DOI: 10.3390/v16111799] [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: 10/01/2024] [Revised: 11/13/2024] [Accepted: 11/19/2024] [Indexed: 11/29/2024] Open
Abstract
(1) Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease. Although the changes in the expression levels of microRNAs (miRNAs) in hepatitis B virus-related diseases have been evaluated, no study has evaluated the role of miRNAs in HBV vaccine response in MASLD patients. We aimed to determine the miRNA expression profile in MASLD patients according to HBV vaccine response. (2) Methods: Overall, 100 MASLD patients and 100 controls were included, and anti-HBs levels were measured after three doses of HBV vaccine administration. After collecting blood samples, 22 different miRNA expression profiles were analyzed by RT-PCR analysis, and changes in the expression levels of potential miRNAs were further verified in all study groups. (3) Results: The miR-146a expression level considerably increased in MASLD patients compared to the control group. Furthermore, miR-99a and miR-640 expression levels significantly increased in AntiHBs (-) healthy individuals. (4): Conclusions: miR-146a could be used as the diagnostic marker in MASLD patients. Furthermore, the miR-99a and miR-640 expression levels could predict hepatitis B vaccine response. However, validation studies are required to verify the biomarker potential of miRNAs within a more significant number of patients.
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Affiliation(s)
- Gamze Guney Eskiler
- Department of Medical Biology, Faculty of Medicine, Sakarya University, 54290 Sakarya, Türkiye;
| | - Oguz Karabay
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Sakarya University, 54290 Sakarya, Türkiye;
| | - Mukaddes Tozlu
- Department of Gastroenterology, Faculty of Medicine, Sakarya University, 54290 Sakarya, Türkiye;
| | - Ayhan Aydin
- Department of Internal Sciences, Sakarya University Training and Research Hospital, 54290 Sakarya, Türkiye;
| | - Kaan Furkan Hamarat
- Faculty of Medicine, Sakarya University, 54290 Sakarya, Türkiye; (K.F.H.); (U.A.)
| | - Umut Alkurt
- Faculty of Medicine, Sakarya University, 54290 Sakarya, Türkiye; (K.F.H.); (U.A.)
| | - Asuman Deveci Ozkan
- Department of Medical Biology, Faculty of Medicine, Sakarya University, 54290 Sakarya, Türkiye;
| | - Yasemin Gunduz
- Department of Radiology, Faculty of Medicine, Sakarya University, 54290 Sakarya, Türkiye;
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Al-Rawaf HA, Gabr SA, Iqbal A, Alghadir AH. Circulating microRNAs as potential biomarkers of physical activity in geriatric patients with HCV. BMC Mol Cell Biol 2024; 25:18. [PMID: 39030480 PMCID: PMC11264506 DOI: 10.1186/s12860-024-00514-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 07/09/2024] [Indexed: 07/21/2024] Open
Abstract
BACKGROUND Circulating microRNAs have been implicated in a diverse array of biological and pathological phenomena. Their potential utility as noninvasive biomarkers for screening and diagnosing various diseases has been proposed. OBJECTIVE This study aimed to explore the potential role of the miRNAs miR-122 and miR-486 as molecular biomarkers in the pathogenesis of hepatitis C virus (HCV) infection. Thus, miR-122 and miR-486 were detected in the serum of HCV patients and healthy controls. Moreover, the potential correlations of miR-122 and miR-486 with viral complications, such as physical activity, pain, muscle fatigue, and HCV infection, were identified. METHODS A total of 150 subjects aged 30 to 66 years were included in this study. The patients were classified as patients with chronic hepatitis C virus (CHC) (n = 110) or healthy controls (n = 40). Real-time polymerase chain reaction (PCR) analyses were performed to determine miR-122 and miR-486 expression. Physical activity (PA), pain score, HCV genotyping, viral overload, aspartate transaminase (AST), alanine transaminase (ALT), lactic acid dehydrogenase (LDH), creatine kinase (CK), and antioxidant status were also estimated by using prevalidated questionnaires, PCR, and spectrophotometric analyses. RESULTS Compared with those in normal controls, significant increases in the serum levels of miR-122 and miR-486 were reported in patients with CHC. In physically active CHC patients, there was a significant correlation between the expression of miRNAs and increased alanine transaminase (ALT), aspartate transaminase (AST), fibrosis scores, and inflammation activity, but no association was reported for hepatitis C virus (HCV) RNA or viral load. Additionally, significant decreases in LDH, CK, GSSG, and pain scores and increases in TAC, GSH, and the GSH/GSSG ratio were reported. Moreover, the expression of miR-122 and miR-486 was positively correlated with changes in body mass index (BMI) and liver fibrosis stage, as well as negatively correlated with sex, PA, TAC, GSH, GSSG, and the GSH/GSSG ratio. CONCLUSION MiR-122 and miR-486 expression levels were strongly correlated with physical activity, pain perception, and muscle fatigue biomarkers in HCV-infected patients. These miRNA levels were associated with elevated AST, ALT, fibrosis scores, LDH, CK, and antioxidant status, thus suggesting their potential as biomarkers for disease severity and oxidative stress. However, no correlation was observed with viral load or HCV-RNA expression, thus implying that these miRNAs may impact disease progression and symptoms through host factors, rather than directly affecting viral replication. In summary, the results demonstrated that molecular studies of miR-22 and miR-468 and their associations with PA, pain, adiposity, sex differences, and muscle fatigue, as well as routine biomarkers, could be useful as prognostic nanoninvasive biomarkers, thus providing novel therapeutic targets for CHC infection.
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Affiliation(s)
- Hadeel A Al-Rawaf
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, 11433, Saudi Arabia
| | - Sami A Gabr
- Department of Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Saudi Arabia
| | - Amir Iqbal
- Department of Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Saudi Arabia.
| | - Ahmad H Alghadir
- Department of Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Saudi Arabia
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Zahid S, Malik A, Waqar S, Zahid F, Tariq N, Khawaja AI, Safir W, Gulzar F, Iqbal J, Ali Q. Countenance and implication of Β-sitosterol, Β-amyrin and epiafzelechin in nickel exposed Rat: in-silico and in-vivo approach. Sci Rep 2023; 13:21351. [PMID: 38049552 PMCID: PMC10695965 DOI: 10.1038/s41598-023-48772-4] [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: 12/23/2022] [Accepted: 11/30/2023] [Indexed: 12/06/2023] Open
Abstract
The detrimental impact of reactive oxygen species on D.N.A. repair processes is one of the contributing factors to colon cancer. The idea that oxidative stress may be a significant etiological element for carcinogenesis is currently receiving more and more support. The goal of the current study is to evaluate the anti-inflammatory and anticancer activity of three powerful phytocompounds-sitosterol, amyrin, and epiafzelechin-alone and in various therapeutic combinations against colon cancer to identify the critical mechanisms that mitigate nickel's carcinogenic effect. To evaluate the ligand-protein interaction of four selected components against Vascular endothelial growth factor (VEGF), Matrix metalloproteinase-9 (MMP9) inhibitor and Interleukin-10 (IL-10) molecular docking approach was applied using PyRx bioinformatics tool. For in vivo analysis, hundred albino rats were included, divided into ten groups, each containing ten rats of weight 160-200 g. All the groups were injected with 1 ml/kg nickel intraperitoneally per week for three months, excluding the negative control group. Three of the ten groups were treated with β-sitosterol (100 mg/kg b wt), β-amyrin (100 mg/kg b wt), and epiafzelechin (200 mg/kg b wt), respectively, for one month. The later four groups were fed with combinatorial treatments of the three phyto compounds for one month. The last group was administered with commercial drug Nalgin (500 mg/kg b wt). The biochemical parameters Creatinine, Protein carbonyl, 8-hydroxydeoxyguanosine (8-OHdG), VEGF, MMP-9 Inhibitor, and IL-10 were estimated using ELISA kits and Glutathione (G.S.H.), Superoxide dismutase (S.O.D.), Catalase (C.A.T.) and Nitric Oxide (NO) were analyzed manually. The correlation was analyzed through Pearson's correlation matrix. All the parameters were significantly raised in the positive control group, indicating significant inflammation. At the same time, the levels of the foresaid biomarkers were decreased in the serum in all the other groups treated with the three phytocompounds in different dose patterns. However, the best recovery was observed in the group where the three active compounds were administered concomitantly. The correlation matrix indicated a significant positive correlation of IL-10 vs VEGF (r = 0.749**, p = 0.009), MMP-9 inhibitor vs SOD (r = 0.748**, p = 0.0 21). The study concluded that the three phytocompounds β-sitosterol, β-amyrin, and epiafzelechin are important anticancer agents which can target the cancerous biomarkers and might be used as a better therapeutic approach against colon cancer soon.
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Affiliation(s)
- Sara Zahid
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan
| | - Arif Malik
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan.
| | - Suleyman Waqar
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan
| | - Fatima Zahid
- Ibadat International University (IIUI), Islamabad, Pakistan
| | - Nusrat Tariq
- M. Islam Medical and Dental College, Gujranwala, Pakistan
| | - Ali Imran Khawaja
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan
| | - Waqas Safir
- Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Sciences and Technology, Xinjiang University, Urumqi, 830046, Xinjiang, China
| | - Faisal Gulzar
- Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan
| | - Javeid Iqbal
- School of Pharmacy, Minhaj University Lahore, Lahore, Pakistan
| | - Qurban Ali
- Department of Plant Breeding and Genetics, Faculty of Agricultural Sciences, University of the Punjab, Lahore, Pakistan.
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Deng K, Xing J, Xu G, Jin B, Wan X, Zheng Y, Du S, Sang X. Urinary biomarkers for hepatocellular carcinoma: current knowledge for clinicians. Cancer Cell Int 2023; 23:239. [PMID: 37833757 PMCID: PMC10571477 DOI: 10.1186/s12935-023-03092-5] [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: 05/29/2023] [Accepted: 10/04/2023] [Indexed: 10/15/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most predominant primary liver cancer, causing many illnesses and deaths worldwide. The insidious clinical presentation, difficulty in early diagnosis, and the highly malignant nature make the prognosis of HCC extremely poor. The complex and heterogeneous pathogenesis of HCC poses significant challenges to developing therapies. Urine-based biomarkers for HCC, including diagnostic, prognostic, and monitoring markers, may be valuable supplements to current tools such as serum α-fetoprotein (AFP) and seem promising for progress in precision medicine. Herein, we reviewed the major urinary biomarkers for HCC and assessed their potential for clinical application. Molecular types, testing platforms, and methods for building multimolecule models in the included studies have shown great diversity, thus providing abundant novel tools for future clinical transformation and applications.
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Affiliation(s)
- Kaige Deng
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China
| | - Jiali Xing
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China
| | - Gang Xu
- Department of Liver Surgery and Liver Transplant Center, West China Hospital of Sichuan University, Chengdu, China
| | - Bao Jin
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China
| | - Xueshuai Wan
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China
| | - Yongchang Zheng
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
| | - Xinting Sang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
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Jordaens S, Zwaenepoel K, Tjalma W, Deben C, Beyers K, Vankerckhoven V, Pauwels P, Vorsters A. Urine biomarkers in cancer detection: A systematic review of preanalytical parameters and applied methods. Int J Cancer 2023; 152:2186-2205. [PMID: 36647333 DOI: 10.1002/ijc.34434] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/25/2022] [Accepted: 12/29/2022] [Indexed: 01/18/2023]
Abstract
The aim of this review was to explore the status of urine sampling as a liquid biopsy for noninvasive cancer research by reviewing used preanalytical parameters and protocols. We searched two main health sciences databases, PubMed and Web of Science. From all eligible publications (2010-2022), information was extracted regarding: (a) study population characteristics, (b) cancer type, (c) urine preanalytics, (d) analyte class, (e) isolation method, (f) detection method, (g) comparator used, (h) biomarker type, (i) conclusion and (j) sensitivity and specificity. The search query identified 7835 records, of which 924 unique publications remained after screening the title, abstract and full text. Our analysis demonstrated that many publications did not report information about the preanalytical parameters of their urine samples, even though several other studies have shown the importance of standardization of sample handling. Interestingly, it was noted that urine is used for many cancer types and not just cancers originating from the urogenital tract. Many different types of relevant analytes have been shown to be found in urine. Additionally, future considerations and recommendations are discussed: (a) the heterogeneous nature of urine, (b) the need for standardized practice protocols and (c) the road toward the clinic. Urine is an emerging liquid biopsy with broad applicability in different analytes and several cancer types. However, standard practice protocols for sample handling and processing would help to elaborate the clinical utility of urine in cancer research, detection and disease monitoring.
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Affiliation(s)
- Stephanie Jordaens
- Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Wilrijk, Belgium.,Novosanis NV, Wijnegem, Belgium
| | - Karen Zwaenepoel
- Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Wilrijk, Belgium.,Laboratory of Pathological Anatomy, Antwerp University Hospital (UZA), Edegem, Belgium
| | - Wiebren Tjalma
- Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Wilrijk, Belgium.,Multidisciplinary Breast Clinic, Gynecological Oncology Unit, Department of Obstetrics and Gynecology, Antwerp University Hospital (UZA), Edegem, Belgium
| | - Christophe Deben
- Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Wilrijk, Belgium
| | | | - Vanessa Vankerckhoven
- Novosanis NV, Wijnegem, Belgium.,Center for Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium
| | - Patrick Pauwels
- Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Wilrijk, Belgium.,Laboratory of Pathological Anatomy, Antwerp University Hospital (UZA), Edegem, Belgium
| | - Alex Vorsters
- Center for Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium
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Jafari A, Karimabadi K, Rahimi A, Rostaminasab G, Khazaei M, Rezakhani L, Ahmadi jouybari T. The Emerging Role of Exosomal miRNAs as Biomarkers for Early Cancer Detection: A Comprehensive Literature Review. Technol Cancer Res Treat 2023; 22:15330338231205999. [PMID: 37817634 PMCID: PMC10566290 DOI: 10.1177/15330338231205999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 09/10/2023] [Accepted: 09/13/2023] [Indexed: 10/12/2023] Open
Abstract
A significant number of cancer-related deaths are recorded globally each year, despite attempts to cure this illness. Medical science is working to develop new medication therapies as well as to find ways to identify this illness as early as possible, even using noninvasive techniques. Early detection of cancer can greatly aid its treatment. Studies into cancer diagnosis and therapy have recently shifted their focus to exosome (EXO) biomarkers, which comprise numerous RNA and proteins. EXOs are minuscule goblet vesicles that have a width of 30 to 140 nm and are released by a variety of cells, including immune, stem, and tumor cells, as well as bodily fluids. According to a growing body of research, EXOs, and cancer appear to be related. EXOs from tumors play a role in the genetic information transfer between tumor and basal cells, which controls angiogenesis and fosters tumor development and spread. To identify malignant activities early on, microRNAs (miRNAs) from cancers can be extracted from circulatory system EXOs. Specific markers can be used to identify cancer-derived EXOs containing miRNAs, which may be more reliable and precise for early detection. Conventional solid biopsy has become increasingly limited as precision and personalized medicine has advanced, while liquid biopsy offers a viable platform for noninvasive diagnosis and prognosis. Therefore, the use of body fluids such as serum, plasma, urine, and salivary secretions can help find cancer biomarkers using technologies related to EXOs.
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Affiliation(s)
- Ali Jafari
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Keyvan Karimabadi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Aso Rahimi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Gelavizh Rostaminasab
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mozafar Khazaei
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Leila Rezakhani
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Touraj Ahmadi jouybari
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Zhou Y, Liu F, Ma C, Cheng Q. Involvement of microRNAs and their potential diagnostic, therapeutic, and prognostic role in hepatocellular carcinoma. J Clin Lab Anal 2022; 36:e24673. [PMID: 36036748 PMCID: PMC9551129 DOI: 10.1002/jcla.24673] [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: 04/11/2022] [Revised: 07/01/2022] [Accepted: 08/13/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) accounts for 85%-90% of primary liver cancer. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting the 3'UTR of mRNA. Abnormal expression and regulation of miRNAs are involved in the occurrence and progression of HCC, and miRNAs can also play a role in the diagnosis and treatment of HCC as oncogenes or tumor suppressors. METHODS In the past decades, a large number of studies have shown that miRNAs play an essential regulatory role in HCC and have potential as biomarkers for HCC. We reviewed the literature to summarize these studies. RESULTS By reviewing the literature, we retrospected the roles of miRNAs in the development, diagnosis, treatment, and prognosis of HCC, and put forward prospects for the further research on miRNAs in the precision treatment of HCC. CONCLUSION MicroRNAs are important regulators and biomarkers in the occurrence, progression, outcome, and treatment of HCC, and can provide new targets and strategies for improving the therapeutic effect of HCC.
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Affiliation(s)
- Yilong Zhou
- Department of Surgery, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China
| | - Fan Liu
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong, China
| | - Chunyang Ma
- Department of Surgery, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China
| | - Qiong Cheng
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, China
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Sun C, Shi C, Duan X, Zhang Y, Wang B. Exosomal microRNA-618 derived from mesenchymal stem cells attenuate the progression of hepatic fibrosis by targeting Smad4. Bioengineered 2022; 13:5915-5927. [PMID: 35199612 PMCID: PMC8973762 DOI: 10.1080/21655979.2021.2023799] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Hepatic fibrosis (HF) is a pathological phenomenon that occurs during the process of long-term damage and repair in the liver. This condition will lead to the development of cirrhosis and even liver cancer if untreated. Previous evidence has shown that exosomes derived from mesenchymal stem cells (MSCs), carrying microRNAs (miRs), can affect the pathogenesis of HF. Therefore, the present study aimed to identify novel exosomal miRs derived from MSCs that play a critical role in the progression of HF. Next, the expression data of differentially expressed miRs (DEMs) of patients with liver cirrhosis and healthy controls were obtained from the Gene Expression Omnibus dataset. DEMs were analyzed using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, to further confirm the function of exosomal miR-618 derived from MSCs on the pathogenesis of HF in vivo, a mouse model of HF was established. The results of the present study suggested that a close associated existed between DEMs and HF. Based on the results of the bioinformatics analysis, miR-618 was one of the main downregulated miRs involved in cirrhosis. In addition, miR-618 could be transferred from MSCs to LX-2 cells via exosomes; exosomal miR-618 derived from MSCs inhibited the viability and migration of LX-2 cells that were treated with TGF-β. Furthermore, exosomal miR-618 derived from MSCs attenuated the progression of HF via targeting Smad4. These findings indicated that treatment of exosomal miR-618 derived from MSCs might serve as a new strategy for HF.
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Affiliation(s)
- Chao Sun
- Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Cuicui Shi
- Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoyan Duan
- Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi Zhang
- Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Baocan Wang
- Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Gibriel AA, Ismail MF, Sleem H, Zayed N, Yosry A, El-Nahaas SM, Shehata NI. Diagnosis and staging of HCV associated fibrosis, cirrhosis and hepatocellular carcinoma with target identification for miR-650, 552-3p, 676-3p, 512-5p and 147b. Cancer Biomark 2022; 34:413-430. [DOI: 10.3233/cbm-210456] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND: Chronic HCV infection progresses to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The latter represents the third most common cause for cancer mortality. Currently, there is no reliable non-invasive biomarker for diagnosis of HCV mediated disorders. OBJECTIVE: Profiling expression signature for circulatory miRNAs in the plasma of 167 Egyptian patients (40 healthy, 48 HCV fibrotic, 39 HCV cirrhotic and 40 HCV-HCC cases). METHODS: QRTPCR was used to quantify expression signature for circulatory miRNAs. RESULTS: MiR-676 and miR-650 were powerful in discriminating cirrhotic and late fibrosis from HCC. MiR-650 could distinguish mild (f0-f1) and advanced (f2-f3) fibrosis from HCC cases. MiR-650 and miR-147b could distinguish early fibrosis from healthy controls meanwhile miR-676 and miR-147b could effectively distinguish between mild chronic and (f1-f3) cases from healthy individuals. All studied miRNAs, except miR-512, can differentiate between (f0-f3) cases and healthy controls. Multivariate logistic regression revealed three potential miRNA panels for effective differentiation of HCC, cirrhotic and chronic liver cases. MiR-676-3p and miR-512-5p were significantly correlated in (f1-f3) fibrosis meanwhile miR-676 and miR-512 could differentiate between cirrhosis and (f0-f3) cases. Both miR-650 and miR-512-5p were positively correlated in the cirrhotic group and in (f0-f4) group. Putative targets for investigated miRNAs were also determined. CONCLUSIONS: Investigated miRNAs could assist in staging and diagnosis of HCV associated disorders.
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Affiliation(s)
- Abdullah Ahmed Gibriel
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt
| | - Manal Fouad Ismail
- Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Hameis Sleem
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt
| | - Naglaa Zayed
- Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ayman Yosry
- Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Saeed M. El-Nahaas
- Endemic Medicine Department and Hepatology Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
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Natu A, Singh A, Gupta S. Hepatocellular carcinoma: Understanding molecular mechanisms for defining potential clinical modalities. World J Hepatol 2021; 13:1568-1583. [PMID: 34904030 PMCID: PMC8637668 DOI: 10.4254/wjh.v13.i11.1568] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 05/12/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
Liver cancer is the sixth most commonly occurring cancer and costs millions of lives per year. The diagnosis of hepatocellular carcinoma (HCC) has relied on scanning techniques and serum-based markers such as α-fetoprotein. These measures have limitations due to their detection limits and asymptomatic conditions during the early stages, resulting in late-stage cancer diagnosis where targeted chemotherapy or systemic treatment with sorafenib is offered. However, the aid of conventional therapy for patients in the advanced stage of HCC has limited outcomes. Thus, it is essential to seek a new treatment strategy and improve the diagnostic techniques to manage the disease. Researchers have used the omics profile of HCC patients for sub-classification of tissues into different groups, which has helped us with prognosis. Despite these efforts, a promising target for treatment has not been identified. The hurdle in this situation is genetic and epigenetic variations in the tumor, leading to disparities in response to treatment. Understanding reversible epigenetic changes along with clinical traits help to define new markers for patient categorization and design personalized therapy. Many clinical trials of inhibitors of epigenetic modifiers (also known as epi-drugs) are in progress. Epi-drugs like azacytidine or belinostat are already approved for other cancer treatments. Furthermore, epigenetic changes have also been observed in drug-resistant HCC tumors. In such cases, combinatorial treatment of epi-drugs with systemic therapy or trans-arterial chemoembolization might re-sensitize resistant cells.
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Affiliation(s)
- Abhiram Natu
- Epigenetics and Chromatin Biology Group, Gupta Laboratory, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India
- Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400085, Maharashtra, India
| | - Anjali Singh
- Epigenetics and Chromatin Biology Group, Gupta Laboratory, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India
- Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400085, Maharashtra, India
| | - Sanjay Gupta
- Epigenetics and Chromatin Biology Group, Gupta Laboratory, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India
- Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400085, Maharashtra, India
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11
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MiRNAs and Cancer: Key Link in Diagnosis and Therapy. Genes (Basel) 2021; 12:genes12081289. [PMID: 34440464 PMCID: PMC8395027 DOI: 10.3390/genes12081289] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 08/18/2021] [Accepted: 08/20/2021] [Indexed: 02/07/2023] Open
Abstract
Since the discovery of the first microRNA (miRNA), the exploration of miRNA biology has come to a new era in recent decades. Monumental studies have proven that miRNAs can be dysregulated in different types of cancers and the roles of miRNAs turn out to function to either tumor promoters or tumor suppressors. The interplay between miRNAs and the development of cancers has grabbed attention of miRNAs as novel tools and targets for therapeutic attempts. Moreover, the development of miRNA delivery system accelerates miRNA preclinical implications. In this review, we depict recent advances of miRNAs in cancer and discuss the potential diagnostic or therapeutic approaches of miRNAs.
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12
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Guan MC, Ouyang W, Wang MD, Liang L, Li N, Fu TT, Shen F, Lau WY, Xu QR, Huang DS, Zhu H, Yang T. Biomarkers for hepatocellular carcinoma based on body fluids and feces. World J Gastrointest Oncol 2021; 13:351-365. [PMID: 34040698 PMCID: PMC8131906 DOI: 10.4251/wjgo.v13.i5.351] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/18/2021] [Accepted: 04/14/2021] [Indexed: 02/06/2023] Open
Abstract
Novel non-/minimally-invasive and effective approaches are urgently needed to supplement and improve current strategies for diagnosis and management of hepatocellular carcinoma (HCC). Overwhelming evidence from published studies on HCC has documented that multiple molecular biomarkers detected in body fluids and feces can be utilized in early-diagnosis, predicting responses to specific therapies, evaluating prognosis before or after therapy, as well as serving as novel therapeutic targets. Detection and analysis of proteins, metabolites, circulating nucleic acids, circulating tumor cells, and extracellular vesicles in body fluids (e.g., blood and urine) and gut microbiota (e.g., in feces) have excellent capabilities to improve different aspects of management of HCC. Numerous studies have been devoted in identifying more promising candidate biomarkers and therapeutic targets for diagnosis, treatment, and monitoring responses of HCC to conventional therapies, most of which may improve diagnosis and management of HCC in the future. This review aimed to summarize recent advances in utilizing these biomarkers in HCC and discuss their clinical significance.
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Affiliation(s)
- Ming-Cheng Guan
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Wei Ouyang
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China
| | - Lei Liang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310000, Zhejiang Province, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
| | - Na Li
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Ting-Ting Fu
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China
| | - Wan-Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Qiu-Ran Xu
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310000, Zhejiang Province, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
| | - Dong-Sheng Huang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310000, Zhejiang Province, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
| | - Hong Zhu
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310000, Zhejiang Province, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
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13
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Hoshino I. The usefulness of microRNA in urine and saliva as a biomarker of gastroenterological cancer. Int J Clin Oncol 2021; 26:1431-1440. [PMID: 33835295 DOI: 10.1007/s10147-021-01911-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 03/24/2021] [Indexed: 12/21/2022]
Abstract
MicroRNA (miR) is a type of short non-coding RNA comprising 21-25 nucleotides. While it has been researched widely, its relationship with cancer was clarified recently and it was found to play a significant role in the development and progression of cancer. Furthermore, miR can remain stable for relatively long periods in the blood by being present in exosomes (extracellular microvesicles) or by forming a complex with the Ago2 protein, which gives rise to cancer-specific miR. It is known that miR can indicate the presence and extent of cancer progression. Several reports have proved that miR in urine and saliva is detected in urinary and oral cancer, respectively, and recent studies have also shown it to be present in cases of gastroenterological cancer, showing evidence of it being a biomarker for cancer. To gather further knowledge on this topic, this review aims to summarize the usefulness of urinary and salivary miR as a biomarker for gastroenterological cancer and discuss its existence, stability mechanism, and direction of future research. The findings will be relevant for physicians and oncologists who routinely treat patients with gastric cancers.
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Affiliation(s)
- Isamu Hoshino
- Division of Gastroenterological Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, 260-8717, Japan.
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14
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Circulating miR-618 Has Prognostic Significance in Patients with Metastatic Colon Cancer. ACTA ACUST UNITED AC 2021; 28:1204-1215. [PMID: 33804070 PMCID: PMC8025826 DOI: 10.3390/curroncol28020116] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/28/2021] [Accepted: 03/11/2021] [Indexed: 01/05/2023]
Abstract
The present study evaluated the prognostic role of circulating miRNA-618 in patients with metastatic colon cancer (mCC) and whether miR-618 gene rs2682818 single nucleotide polymorphisms (SNP) are associated with colon cancer susceptibility and expression levels of mature miR-618. In total, 104 patients with mCC before starting the chemotherapy were investigated. The expression status of circulating miR-618 in mCC was evaluated by quantitative PCR. TaqMan PCR assay was used for rs2682818 SNP genotyping. miR-618 was overexpressed in serum of mCC patients. Patients with high and intermediate expression of miR-618 had a significantly longer mean overall survival (OS) of 21 months than patients with low expression—16 months. In addition, multivariate Cox regression analysis confirmed the association between high/intermediate levels of miRNA-618 and longer OS, HR = 0.51, 95% CI: 0.30–0.86, p = 0.012. miR-618 rs2682818 SNP significantly decreased the risk of colon cancer susceptibility in both heterozygous codominant (AC vs. CC, OR = 0.39, 95% CI: 0.17–0.88, p = 0.024) and overdominant (AC vs. CC + AA, OR = 0.37, 95% CI: 0.16–0.85, p = 0.018) genetic models. Our data suggest that circulating miRNA-618 could be useful as a prognostic biomarker in mCC. Patients harboring AC rs2682818 genotype have a decreased risk for colon cancer in comparison with patients with CC and AA genotypes.
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15
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Yang L, Wei C, Li Y, He X, He M. miR-224 is an early-stage biomarker of hepatocellular carcinoma with miR-224 and miR-125b as prognostic biomarkers. Biomark Med 2020; 14:1485-1500. [PMID: 33155836 DOI: 10.2217/bmm-2020-0099] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Aim: The aim was to systematically investigate the miRNA biomarkers for early diagnosis of hepatocellular carcinoma (HCC). Materials & methods: A systematic review and meta-analysis of miRNA expression in HCC were performed. Results: A total of 4903 cases from 30 original studies were comprehensively analyzed. The sensitivity and specificity of miR-224 in discriminating early-stage HCC patients from benign lesion patients were 0.868 and 0.792, which were superior to α-fetoprotein. Combined miR-224 with α-fetoprotein, the sensitivity and specificity were increased to 0.882 and 0.808. Prognostic survival analysis showed low expression of miR-125b and high expression of miR-224 were associated with poor prognosis. Conclusion: miR-224 had a prominent diagnostic efficiency in early-stage HCC, with miR-224 and miR-125b being valuable in the prognostic diagnosis.
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Affiliation(s)
- Lichao Yang
- School of Public Health, Guangxi Medical University, Nanning 530021, China
| | - Chunmeng Wei
- Nanning Municipal Center for Disease Control & Prevention, Nanning 530021, China
| | - Yasi Li
- College of Global Public Health, New York University, NY 10003, USA
| | - Xiao He
- School of Public Health, Guilin Medical School, Guilin 541100, China
| | - Min He
- School of Public Health, Guangxi Medical University, Nanning 530021, China.,Key Laboratory of High-Incidence Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning 530021, China.,Laboratory Animal Center, Guangxi Medical University, Nanning 530021, China
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16
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Zhang S, Zhou Y, Wang Y, Wang Z, Xiao Q, Zhang Y, Lou Y, Qiu Y, Zhu F. The mechanistic, diagnostic and therapeutic novel nucleic acids for hepatocellular carcinoma emerging in past score years. Brief Bioinform 2020; 22:1860-1883. [PMID: 32249290 DOI: 10.1093/bib/bbaa023] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 02/09/2020] [Accepted: 02/12/2020] [Indexed: 02/07/2023] Open
Abstract
Despite The Central Dogma states the destiny of gene as 'DNA makes RNA and RNA makes protein', the nucleic acids not only store and transmit genetic information but also, surprisingly, join in intracellular vital movement as a regulator of gene expression. Bioinformatics has contributed to knowledge for a series of emerging novel nucleic acids molecules. For typical cases, microRNA (miRNA), long noncoding RNA (lncRNA) and circular RNA (circRNA) exert crucial role in regulating vital biological processes, especially in malignant diseases. Due to extraordinarily heterogeneity among all malignancies, hepatocellular carcinoma (HCC) has emerged enormous limitation in diagnosis and therapy. Mechanistic, diagnostic and therapeutic nucleic acids for HCC emerging in past score years have been systematically reviewed. Particularly, we have organized recent advances on nucleic acids of HCC into three facets: (i) summarizing diverse nucleic acids and their modification (miRNA, lncRNA, circRNA, circulating tumor DNA and DNA methylation) acting as potential biomarkers in HCC diagnosis; (ii) concluding different patterns of three key noncoding RNAs (miRNA, lncRNA and circRNA) in gene regulation and (iii) outlining the progress of these novel nucleic acids for HCC diagnosis and therapy in clinical trials, and discuss their possibility for clinical applications. All in all, this review takes a detailed look at the advances of novel nucleic acids from potential of biomarkers and elaboration of mechanism to early clinical application in past 20 years.
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Affiliation(s)
- Song Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital in Zhejiang University, China.,College of Pharmaceutical Sciences in Zhejiang University, China
| | - Ying Zhou
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital in Zhejiang University, China
| | - Yanan Wang
- School of Life Sciences in Nanchang University, China
| | - Zhengwen Wang
- College of Pharmaceutical Sciences in Zhejiang University, China
| | - Qitao Xiao
- College of Pharmaceutical Sciences in Zhejiang University, China
| | - Ying Zhang
- College of Pharmaceutical Sciences in Zhejiang University, China
| | - Yan Lou
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital in Zhejiang University, China
| | - Yunqing Qiu
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital in Zhejiang University, China
| | - Feng Zhu
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital in Zhejiang University, China.,College of Pharmaceutical Sciences in Zhejiang University, China
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Zhang W, Zhang XJ, Chao SY, Chen SJ, Zhang ZJ, Zhao J, Lv YN, Yao JJ, Bai YY. Update on urine as a biomarker in cancer: a necessary review of an old story. Expert Rev Mol Diagn 2020; 20:477-488. [PMID: 32212972 DOI: 10.1080/14737159.2020.1743687] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Introduction: Cancer causes thousands of deaths worldwide each year. Therefore, monitoring of health status and the early diagnosis of cancer using noninvasive assays, such as the analysis of molecular biomarkers in urine, is essential. However, effective biomarkers for early diagnosis of cancer have not been established in many types of cancer.Areas covered: In this review, we discuss recent findings with regard to the use of urine composition as a biomarker in eleven types of cancer. We also highlight the use of urine biomarkers for improving early diagnosis.Expert opinion: Urinary biomarkers have been applied for clinical application of early diagnosis. The main limitation is a lack of integrated approaches for identification of new biomarkers in most cancer. The utilization of urinary biomarker detection will be promoted by improved detection methods and new data from different types of cancers. With the development of precision medicine, urinary biomarkers will play an increasingly important clinical role. Future early diagnosis would benefit from changes in the utilization of urinary biomarkers.
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Affiliation(s)
- Wei Zhang
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China
| | - Xiao Jian Zhang
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China
| | - Shen Yan Chao
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China
| | - Su Juan Chen
- Synthetic Biology Engineering Lab of Henan Province, School of Sciences and Technology, Xinxiang Medical University, Henan, China
| | - Zi Jing Zhang
- Institute of Animal Husbandry and Veterinary Science, Henan Academy of Agricultural Sciences, Zhengzhou, Henan, PR China
| | - Jian Zhao
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China
| | - Ya Nan Lv
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China
| | - Jing Jie Yao
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China
| | - Yue Yu Bai
- Animal Health Supervision in Henan Province, Zhengzhou, Henan, PR China
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Hasham K, Ahmed N, Zeshan B. Circulating microRNAs in oncogenic viral infections: potential diagnostic biomarkers. SN APPLIED SCIENCES 2020. [DOI: 10.1007/s42452-020-2251-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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19
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Ziogas IA, Sioutas G, Mylonas KS, Tsoulfas G. Role of MicroRNA in the Diagnosis and Management of Hepatocellular Carcinoma. Microrna 2020; 9:25-40. [PMID: 31218966 DOI: 10.2174/2211536608666190619155406] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 03/11/2019] [Accepted: 05/06/2019] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors in the world and comes third in cancer-induced mortality. The need for improved and more specific diagnostic methods that can detect early-stage disease is immense, as it is amenable to curative modalities, while advanced HCC is associated with low survival rates. microRNA (miRNA) expression is deregulated in HCC and this can be implemented both diagnostically and therapeutically. OBJECTIVE To provide a concise review on the role of miRNA in diagnosis, prognosis, and treatment of HCC. METHODS We conducted a comprehensive review of the PubMed bibliographic database. RESULTS Multiple miRNAs are involved in the pathogenesis of HCC. Measurement of the levels of these miRNAs either in tumor tissue or in the blood constitutes a promising diagnostic, as well as prognostic tool. OncomiRs are miRNAs that promote tumorigenesis, thus inhibiting them by administering antagomiRs is a promising treatment option. Moreover, replacement of the depleted miRNAs is another potential therapeutic approach for HCC. Modification of miRNA levels may also regulate sensitivity to chemotherapeutic agents. CONCLUSION miRNA play a pivotal role in HCC pathogenesis and once the underlying mechanisms are elucidated, they will become part of everyday clinical practice against HCC.
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Affiliation(s)
- Ioannis A Ziogas
- Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
| | - Georgios Sioutas
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
- Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - Konstantinos S Mylonas
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
- Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Tsoulfas
- 1st Department of Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Abstract
The aim of this study was to investigate the alterations of urinary microRNA (miRNA) expression and explore its clinical significance in patients with chronic hepatitis B (CHB).The expression levels of urinary miRNA were detected by miRNA microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 106 CHB and 40 healthy controls (Ctrl) subjects. The correlation between the levels of miRNA expression and clinical characteristics were analyzed. Receiver-operator characteristic (ROC) curves were generated to determine the specificity and sensitivity of each individual miRNA. MiRNAs expression were further measured by PCR from exosomes, which were isolated from urine samples. LX2 cells were transfected with miRNA inhibitor and accumulation of cytoplasmic lipid droplets was analyzed by Oil Red O staining.miRNA expression profile analysis showed that 22 miRNAs were upregulated and 55 miRNAs were downregulated in CHB patients compared with Ctrl subjects (fold-change>1.5 and P < .05). miR-92b-3p, miR-770-5p, miR-5196-5p, and miR-7855-5p were significantly higher (P < .0001) in CHB subjects than in Ctrl subjects. ROC curve analysis showed that these four miRNAs were sensitive and specific enough to distinguish CHB and Ctrl subjects. The levels of miR-92b-3p expression were negatively correlated with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and APOA-1. Moreover, in vitro experiments indicated that inhibition of miR-92b-3p increased lipid droplet formation in LX2 cells.Aberrant expression of miRNAs has been observed in urine of CHB patients. Our findings may provide novel insights into the pathogenesis of CHB and may assist in the diagnosis of patients with CHB.
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Affiliation(s)
- Jia-Wei Shang
- Research Center for Traditional Chinese Medicine Complexity System, Institute of Interdisciplinary Integrative Medicine Research
| | - Xiu-Li Yan
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China
| | - Hui Zhang
- Research Center for Traditional Chinese Medicine Complexity System, Institute of Interdisciplinary Integrative Medicine Research
| | - Shi-Bing Su
- Research Center for Traditional Chinese Medicine Complexity System, Institute of Interdisciplinary Integrative Medicine Research
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Does miR-618 rs2682818 variant affect cancer susceptibility? Evidence from 10 case-control studies. Biosci Rep 2019; 39:BSR20190741. [PMID: 31383788 PMCID: PMC6706600 DOI: 10.1042/bsr20190741] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 07/11/2019] [Accepted: 08/02/2019] [Indexed: 12/17/2022] Open
Abstract
Piles of evidence have supported the relationship between miR-618 rs2682818 polymorphism and tumorigenesis, but the conclusion remains inconsistent. In the present study, we conducted a meta-analysis to sniff out the potential risk between miR-618 rs2682818 and overall cancers. Crude odds ratios (ORs) and 95% confidence intervals (CIs) analyzed by Z-test were employed to estimate the potential interrelation in five genetic models. We also prospected how the rs2682818 affects the second structure of miR-618. Finally, 10 independent studies meet the enrolled criteria, along with 4099 cancer cases and 5057 healthy controls. Overall, no exceeding interrelation was sniffed out in the pooled data among five inherited models, as well as stratified analyses. Whereas, the enhanced cancer risk of miR-618 rs2682818 variant stratified by breast cancer was revealed, in heterozygote genetic model (AC vs. CC: OR = 1.291, 95%CI = 1.012-1.648, P = 0.040) and dominant contrast model (AA + AC vs. CC: OR = 1.280, 95%CI = 1.009-1.623, P = 0.042). The second structure prediction result shown that the mutant A allele might change the first stem-loop of miR-618, and the free energy of it would turn from -39.1 to -35.1 kcal/mol. All in all, our meta-analysis had successfully chased down that miR-618 rs2682818 polymorphism is not linked with overall cancer risk, but in the dominant genotype of breast cancer.
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Temilola DO, Wium M, Coulidiati TH, Adeola HA, Carbone GM, Catapano CV, Zerbini LF. The Prospect and Challenges to the Flow of Liquid Biopsy in Africa. Cells 2019; 8:E862. [PMID: 31404988 PMCID: PMC6721679 DOI: 10.3390/cells8080862] [Citation(s) in RCA: 17] [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: 07/16/2019] [Revised: 07/30/2019] [Accepted: 08/03/2019] [Indexed: 12/24/2022] Open
Abstract
Liquid biopsy technologies have the potential to transform cancer patient management as it offers non-invasive diagnosis and real-time monitoring of disease progression and treatment responses. The use of liquid biopsy for non-invasive cancer diagnosis can have pivotal importance for the African continent where access to medical infrastructures is limited, as it eliminates the need for surgical biopsies. To apply liquid biopsy technologies in the African setting, the influence of environmental and population genetic factors must be known. In this review, we discuss the use of circulating tumor cells, cell-free nucleic acids, extracellular vesicles, protein, and other biomolecules in liquid biopsy technology for cancer management with special focus on African studies. We discussed the prospect, barriers, and other aspects that pose challenges to the use of liquid biopsy in the African continent.
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Affiliation(s)
- Dada Oluwaseyi Temilola
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town 7925, South Africa
- Integrative Biomedical Sciences Division, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
| | - Martha Wium
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town 7925, South Africa
| | - Tangbadioa Herve Coulidiati
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town 7925, South Africa
- Training and Research unit in Sciences and Technology, University Norbert Zongo, P.O. Box 376, Koudougou 376, Burkina Faso
| | - Henry Ademola Adeola
- Division of Dermatology, Department of Medicine, Faculty of Health Sciences and Groote Schuur Hospital, University of Cape Town, Cape Town 7925, South Africa
| | - Giuseppina Maria Carbone
- Institute of Oncology Research, Università della Svizzera Italiana, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland
| | - Carlo Vittorio Catapano
- Institute of Oncology Research, Università della Svizzera Italiana, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland
| | - Luiz Fernando Zerbini
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town 7925, South Africa.
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Comparison of plasma and urinary microRNA-483-5p for the diagnosis of adrenocortical malignancy. J Biotechnol 2019; 297:49-53. [PMID: 30940435 DOI: 10.1016/j.jbiotec.2019.03.017] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 03/28/2019] [Accepted: 03/29/2019] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Minimally invasive circulating microRNAs might be used for the preoperative differentiation of adrenocortical carcinoma (ACC) and adrenocortical adenoma (ACA). So far, the best blood-borne microRNA biomarker of ACC is circulating hsa-miR-483-5p. The expression of urinary hsa-miR-483-5p as a non-invasive marker of malignancy and its correlation with plasma hsa-miR-483-5p, has not been investigated, yet. AIM Our aim was to investigate the expression of urinary hsa-miR-483-5p and its correlation with its plasma counterpart. METHODS Plasma and urinary samples from 23 ACC and 23 ACA patients were analysed using real-time RT-qPCR. To evaluate the diagnostic applicability of hsa-miR-483-5p, ROC-analysis was performed. RESULTS Significant overexpression of hsa-miR-483-5p was observed in carcinoma patients' plasma samples compared to adenoma patients' (p < 0.0001, sensitivity: 87%, specificity: 78.3%). In urinary samples, however, no significant difference could be detected between ACC and ACA patients. CONCLUSIONS Plasma hsa-miR-483-5p has been confirmed as significantly overexpressed in adrenocortical cancer patients and thus might be exploited as a minimally invasive preoperative marker of malignancy. The applicability of urinary hsa-miR-483-5p for the diagnosis of adrenocortical malignancy could not be confirmed.
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Świtlik WZ, Bielecka-Kowalska A, Karbownik MS, Kordek R, Jabłkowski M, Szemraj J. Forms of diagnostic material as sources of miRNA biomarkers in hepatocellular carcinoma: a preliminary study. Biomark Med 2019; 13:523-534. [PMID: 30854869 DOI: 10.2217/bmm-2018-0485] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Aim: To assess the diagnostic value of selected miRNAs from various material collected from hepatocellular carcinoma (HCC) patients. Patients & methods: Tissue, serum, urine and fecal samples from HCC patients and healthy individuals were screened for associated miRNAs using microarray analysis; the selected miRNAs were then validated by real time-quantitative PCR on 65 patients. Results: Serum miR-122, a combination of serum miR-155 with miR-885-5p, a combination of urinary miR-532-3p with miR-765, and fecal miR-320a displayed 100% efficiency in discriminating patients from controls. A combination of urinary miR-532-3p and miR-765 allowed patients with neoplastic grade G3 to be distinguished from those with G1 and G2. Conclusion: Additionally to serum, urine and feces also appeared to be valuable source of potential HCC noninvasive miRNA biomarkers.
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Affiliation(s)
- Weronika Zofia Świtlik
- Department of Medical Biochemistry, Medical University of Lodz, Mazowiecka Street 6/8 92-215 Lodz, Poland.,Department of Biochemistry, Faculty of Agriculture & Biology, Warsaw University of Life Sciences - SGGW, Nowoursynowska Street 159, 02-776 Warsaw, Poland
| | | | - Michał Seweryn Karbownik
- Department of Pharmacology & Toxicology, Medical University of Lodz, Zeligowskiego Street 7/9, 90-752 Lodz, Poland
| | - Radzisław Kordek
- Department of Pathology Chair of Oncology, Medical University of Lodz, Pomorska Street 251, 92-213 Lodz, Poland
| | - Maciej Jabłkowski
- Department of Infectious & Liver Diseases, Medical University of Lodz, Kniaziewicza Street 1/5, 91-347 Lodz, Poland
| | - Janusz Szemraj
- Department of Medical Biochemistry, Medical University of Lodz, Mazowiecka Street 6/8 92-215 Lodz, Poland.,BioNanoPark Laboratories, Lodz Regional Park of Science & Technologies, Dubois Street 114/116, 93-465, Lodz, Poland
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Shi J, Gong L, Chen L, Luo J, Song G, Xu J, Lv Z, Tao H, Xia Y, Ye Z. miR-618 Suppresses Metastasis in Gastric Cancer by Downregulating the Expression of TGF-β2. Anat Rec (Hoboken) 2019; 302:931-940. [PMID: 30737902 DOI: 10.1002/ar.24083] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2017] [Revised: 10/17/2018] [Accepted: 10/28/2018] [Indexed: 11/07/2022]
Abstract
Recent studies have demonstrated that microRNAs regulate gene expression and are related to cancer progression. Increasing evidence shows that miR-618 plays an important role in a variety of tumors, including thyroid carcinomas, breast cancer and lymphoma cancer. However, no studies have examined the expression or function of miR-618 in gastric cancer (GC). In this study, we examined the effects and molecular mechanisms of miR-618 in GC. We compared the expression levels of miR-618 in 90 paired GC tissues and adjacent noncancerous tissues. Cell cycle, apoptosis and transwell assays were performed in GC cells with miR-618 mimic or inhibitor in vitro. We first used quantitative PCR(qPCR) to show that miR-618 expression levels were downregulated in GC tissues, which showed statistical significance. Next we used transwell assays to prove that miR-618 suppressed the invasion and migration capacity of GC cells. Furthermore, screening of the miRDB and Target Scan Human databases indicated TGF-β2 as a downstream target of miR-618. In further research, we identified TGF-β2 as a target gene of miR-618 by the luciferase reporter assay. Western blot analysis confirmed that TGF-β2 expression was inversely correlated with miR-618 expression. In situ hybridization showed that miR-618 expression level was downregulated in GC tissues. In conclusion, our findings suggest that miR-618 may function as a tumor suppressor in GC and suppresses metastasis in GC by negatively regulating the transcriptional level of TGF-β2. Anat Rec, 302:931-940, 2019. © 2019 Wiley Periodicals, Inc.
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Affiliation(s)
- Ji Shi
- Zhejiang Province Tongde Hospital, Hangzhou, Zhejiang, China
| | - Lijie Gong
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.,Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
| | - Legao Chen
- Department of Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Jungang Luo
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Guangyuan Song
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Ji Xu
- Department of Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Zhenye Lv
- Department of Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Houquan Tao
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yingjie Xia
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Zaiyuan Ye
- Department of Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
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Ghorbanmehr N, Gharbi S, Korsching E, Tavallaei M, Einollahi B, Mowla SJ. miR-21-5p, miR-141-3p, and miR-205-5p levels in urine-promising biomarkers for the identification of prostate and bladder cancer. Prostate 2019; 79:88-95. [PMID: 30194772 DOI: 10.1002/pros.23714] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Accepted: 08/09/2018] [Indexed: 01/24/2023]
Abstract
BACKGROUND Early detection of cancers improves patients' survival and decreases the treatment cost. Unfortunately, the current methods for diagnosis of bladder and prostate cancers, two most common urothelial malignancies, suffer from a low sensitivity and specificity. MicroRNAs, as a group of endogenously produced non-coding RNAs, regulate gene expression and their expression is observed to be altered in many cancers and cancer progression phenomena. The remarkable stability of microRNAs in biofluids and their unique expression pattern in different pathological conditions make them an appealing, noninvasive diagnostic method in cancer diagnosis. Our objective is to identify microRNAs as biomarkers in urine samples of bladder and prostate cancers to improve the existing diagnostic methods in this field. MATERIALS AND METHODS In this study, urine samples from 110 men with either bladder (n = 45) or prostate (n = 23) cancer, benign prostatic hyperplasia (n = 22) and healthy controls (n = 20) were collected. qPCR was used to evaluate the expression level of miR-21-5p, miR-141-3p, and miR-205-5p in these samples. The sensitivity and specificity of these microRNAs were determined using ROC curve analysis. RESULTS The analysis of the data revealed that miR-21-5p, miR-141-3p, and miR-205-5p are differentially expressed in urine of bladder and prostate cancer patients. All these three microRNAs were upregulated in these samples and they were also able to differentiate benign prostatic hyperplasia from malignant cases. The statistical analyses revealed a good specificity for each individual microRNA. CONCLUSION The results show that these three urine-based microRNAs might be a good choice to implement a specific and non-invasive diagnostic tool for bladder and prostate cancer. The expression pattern of all three microRNAs was particularly useful to distinguish benign and invasive tumors in prostate cases. From the patients' perspective the improvement of the diagnostic situation is awaited eagerly.
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Affiliation(s)
- Nassim Ghorbanmehr
- Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
| | - Sedigheh Gharbi
- Department of Biology, Faculty of Basic Sciences, Shahid Bahonar University of Kerman, Kerman, Iran
| | - Eberhard Korsching
- Institute of Bioinformatics, University Hospital of Münster, University of Münster, Münster, Germany
| | - Mahmood Tavallaei
- Genetic Research Center, Baqiyatallah Medical Sciences University, Tehran, Iran
| | - Behzad Einollahi
- Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Seyed Javad Mowla
- Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
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27
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Sadri Nahand J, Bokharaei-Salim F, Salmaninejad A, Nesaei A, Mohajeri F, Moshtzan A, Tabibzadeh A, Karimzadeh M, Moghoofei M, Marjani A, Yaghoubi S, Keyvani H. microRNAs: Key players in virus-associated hepatocellular carcinoma. J Cell Physiol 2018; 234:12188-12225. [PMID: 30536673 DOI: 10.1002/jcp.27956] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2018] [Accepted: 11/19/2018] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is known as one of the major health problems worldwide. Pathological analysis indicated that a variety of risk factors including genetical (i.e., alteration of tumor suppressors and oncogenes) and environmental factors (i.e., viruses) are involved in beginning and development of HCC. The understanding of these risk factors could guide scientists and clinicians to design effective therapeutic options in HCC treatment. Various viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) via targeting several cellular and molecular pathways involved in HCC pathogenesis. Among various cellular and molecular targets, microRNAs (miRNAs) have appeared as key players in HCC progression. miRNAs are short noncoding RNAs which could play important roles as oncogenes or tumor suppressors in several malignancies such as HCC. Deregulation of many miRNAs (i.e., miR-222, miR-25, miR-92a, miR-1, let-7f, and miR-21) could be associated with different stages of HCC. Besides miRNAs, exosomes are other particles which are involved in HCC pathogenesis via targeting different cargos, such as DNAs, RNAs, miRNAs, and proteins. In this review, we summarize the current knowledge of the role of miRNAs and exosomes as important players in HCC pathogenesis. Moreover, we highlighted HCV- and HBV-related miRNAs which led to HCC progression.
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Affiliation(s)
- Javid Sadri Nahand
- Department of Virology, Iran University of Medical Sciences, Tehran, Iran
| | | | - Arash Salmaninejad
- Drug Applied Research Center, Student Research Committee, Tabriz University of Medical Science, Tabriz, Iran.,Department of Medical Genetics, Medical Genetics Research Center, Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abolfazl Nesaei
- Department of Basic Sciences, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Fatemeh Mohajeri
- Department of Infectious Disease, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
| | - Azadeh Moshtzan
- Department of Infectious Disease, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
| | - Alireza Tabibzadeh
- Department of Virology, Iran University of Medical Sciences, Tehran, Iran
| | | | - Mohsen Moghoofei
- Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Arezo Marjani
- Department of Virology, Iran University of Medical Sciences, Tehran, Iran
| | - Shoeleh Yaghoubi
- Department of Infectious Disease, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
| | - Hossein Keyvani
- Department of Virology, Iran University of Medical Sciences, Tehran, Iran
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28
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Pan WY, Zeng JH, Wen DY, Wang JY, Wang PP, Chen G, Feng ZB. Oncogenic value of microRNA-15b-5p in hepatocellular carcinoma and a bioinformatics investigation. Oncol Lett 2018; 17:1695-1713. [PMID: 30675229 PMCID: PMC6341845 DOI: 10.3892/ol.2018.9748] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 10/12/2018] [Indexed: 02/07/2023] Open
Abstract
miR-15b-5p has frequently been reported to function as a biomarker in some malignancies; however, the function of miR-15b-5p in hepatocellular carcinoma (HCC) and its molecular mechanism are still not well understood. The present study was designed to confirm the clinical value of miR-15b-5p and further explore its underlying molecular mechanism. A comprehensive investigation of the clinical value of miR-15b-5p in HCC was investigated by data mining The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets as well as literature. In addition, intersected target genes of miR-15b-5p were predicted using the miRWalk database and differentially expressed genes of HCC from TCGA. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out. Then, a protein-protein interaction network (PPI) was constructed to reveal the interactions between some hub target genes of miR-15b-5p. The miR-15b-5p expression level in HCC was predominantly overexpressed compared with non-HCC tissues samples (SMD=0.618, 95% CI: 0.207, 1.029; P<0.0001) based on 991 HCC and 456 adjacent non-HCC tissue samples. The pooled summary receiver operator characteristic (SROC) of miR-15b-5p was 0.81 (Q*=0.74), and the pooled sensitivity and specificity of miR-15b-5p in HCC were 72% (95% CI: 69–75%) and 68% (95% CI: 65–72%), respectively. Bioinformatically, 225 overlapping genes were selected as prospective target genes of miR-15b-5p in HCC, and profoundly enriched GO terms and KEGG pathway investigation in silico demonstrated that the target genes were associated with prostate cancer, proximal tubule bicarbonate reclamation, heart trabecula formation, extracellular space, and interleukin-1 receptor activity. Five genes (ACACB, RIPK4, MAP2K1, TLR4 and IGF1) were defined as hub genes from the PPI network. The high expression of miR-15b-5p could play an essential part in hepatocarcinogenesis through diverse regulation approaches.
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Affiliation(s)
- Wen-Ya Pan
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
| | - Jiang-Hui Zeng
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
| | - Dong-Yue Wen
- Department of Ultrasonography, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
| | - Jie-Yu Wang
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
| | - Peng-Peng Wang
- Department of Nursing, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
| | - Gang Chen
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
| | - Zhen-Bo Feng
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
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Ivanovic RF, Viana NI, Morais DR, Moura C, Silva IA, Leite KR, Pontes-Junior J, Nahas WC, Srougi M, Reis ST. miR-618: possible control over TIMP-1 and its expression in localized prostate cancer. BMC Cancer 2018; 18:992. [PMID: 30340564 PMCID: PMC6194613 DOI: 10.1186/s12885-018-4930-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 10/10/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The imbalance between the action of the tissue inhibitors of matrix metalloproteinases (TIMPs) and the matrix metalloproteinases (MMPs) is one component of metastasis physiology. TIMP-1 overrides MMP-9 activity in cancer and might be regulated by miR-618. The aims of this study were to clarify whether TIMP-1 expression is modified by miR-618 and to clarify the effect of miR-618 expression on the invasion of prostate cancer cells. We also studied miR-618 expression in surgical specimens of patients with localized prostate cancer submitted to open radical prostatectomy. METHODS After transfection of miR-618 or its antagonist in DU145 cells, qRT-PCR for TIMP-1/MMP-9 and both ELISA and zymography for MMP-9 were performed. Total miRNA was extracted from surgical specimens of PCa, and miR-618 expression was examined for correlations with Gleason score, pathological status and biochemical recurrence. RESULTS DU145 cells transfected with miR-618 had a 76% reduction in TIMP-1 expression relative to control cells (p = 0.003). miR-618 inhibition reduced MMP-9 expression by 31% (p = 0.032) and MMP-9 absorbance evaluated with ELISA assay (p = 0.06).Zymography suggested higher MMP-9 activity in DU145 cells transfected with miR-618 than those transfected with miR-618 inhibitor, but the difference was not significant (p = 0.55). However, miR-618 expression was lower in surgical specimens of patients with Gleason score > 7 (p = 0.08) and more advanced disease (p = 0.07). CONCLUSIONS In vitro, miR-618 overexpression decreases TIMP-1 and miR-618 inhibition decreases MMP-9, suggesting that miR-618 might be an oncomiR. However, the analysis of clinical samples of localized prostate cancer revealed an inconsistent pattern, as increased miR-618 expression was associated with lower Gleason score and pathological status. Further studies are needed to address whether miR-618 is a context-dependent miRNA.
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Affiliation(s)
- Renato F Ivanovic
- Laboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2nd floor, room 2145, Sao Paulo, 01246-903, Brazil.
| | - Nayara I Viana
- Laboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2nd floor, room 2145, Sao Paulo, 01246-903, Brazil
| | - Denis R Morais
- Laboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2nd floor, room 2145, Sao Paulo, 01246-903, Brazil
| | - Caio Moura
- Laboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2nd floor, room 2145, Sao Paulo, 01246-903, Brazil
| | - Iran A Silva
- Laboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2nd floor, room 2145, Sao Paulo, 01246-903, Brazil
| | - Katia R Leite
- Laboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2nd floor, room 2145, Sao Paulo, 01246-903, Brazil
| | - José Pontes-Junior
- Laboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2nd floor, room 2145, Sao Paulo, 01246-903, Brazil
| | - William C Nahas
- Uro-Oncology Group, Urology Department, University of Sao Paulo Medical School and Institute of Cancer Estate of Sao Paulo (ICESP), Sao Paulo, Brazil
| | - Miguel Srougi
- Laboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2nd floor, room 2145, Sao Paulo, 01246-903, Brazil
| | - Sabrina T Reis
- Laboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2nd floor, room 2145, Sao Paulo, 01246-903, Brazil
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30
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Shaheen NMH, Zayed N, Riad NM, Tamim HH, Shahin RMH, Labib DA, ELsheikh SM, Moneim RA, Yosry A, khalifa RH. Role of circulating miR-182 and miR-150 as biomarkers for cirrhosis and hepatocellular carcinoma post HCV infection in Egyptian patients. Virus Res 2018; 255:77-84. [DOI: 10.1016/j.virusres.2018.07.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 06/23/2018] [Accepted: 07/04/2018] [Indexed: 02/07/2023]
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Identification of potential urine proteins and microRNA biomarkers for the diagnosis of pulmonary tuberculosis patients. Emerg Microbes Infect 2018; 7:63. [PMID: 29636444 PMCID: PMC5893550 DOI: 10.1038/s41426-018-0066-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Revised: 02/23/2018] [Accepted: 03/02/2018] [Indexed: 12/31/2022]
Abstract
This study identified urinary biomarkers for tuberculosis (TB) diagnosis. The urine proteomic profiles of 45 pulmonary tuberculosis patients prior to anti-TB treatment and 45 healthy controls were analyzed and compared using two-dimensional electrophoresis with matrix-assisted laser desorption/ionization time of flight mass spectrometry. Nineteen differentially expressed proteins were identified preliminarily, and western blotting and qRT-PCR were performed to confirm these changes at the translational and transcriptional levels, respectively, using samples from 122 additional pulmonary tuberculosis patients and 73 additional healthy controls. Two proteins, mannose-binding lectin 2 and a 35-kDa fragment of inter-α-trypsin inhibitor H4, exhibited the highest differential expression. We constructed a protein-microRNA interaction network that primarily involved complement and inflammatory responses. Eleven microRNAs from microRNA-target protein interactions were screened and validated using qRT-PCR with some of the above samples, including 97 pulmonary tuberculosis patients and 48 healthy controls. Only miR-625-3p exhibited significant differential expression (p < 0.05). miR-625-3p was increased to a greater extent in samples of smear-positive than smear-negative patients. miR-625-3p was predicted to target mannose-binding lectin 2 protein. A binary logistic regression model based on miR-625-3p, mannose-binding lectin 2, and inter-α-trypsin inhibitor H4 was further established. This three-biomarker combination exhibited better performance for tuberculosis diagnosis than individual biomarkers or any two-biomarker combination and generated a diagnostic sensitivity of 85.87% and a specificity of 87.50%. These novel urine biomarkers may significantly improve tuberculosis diagnosis.
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Catapano F, Domingos J, Perry M, Ricotti V, Phillips L, Servais L, Seferian A, Groot ID, Krom YD, Niks EH, Verschuuren JJ, Straub V, Voit T, Morgan J, Muntoni F. Downregulation of miRNA-29, -23 and -21 in urine of Duchenne muscular dystrophy patients. Epigenomics 2018; 10:875-889. [PMID: 29564913 DOI: 10.2217/epi-2018-0022] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
AIM To study the signature of 87 urinary miRNAs in Duchenne muscular dystrophy (DMD) patients, select the most dysregulated and determine statistically significant differences in their expression between controls, ambulant (A) and nonambulant (NA) DMD patients, and patients on different corticosteroid regimens. Patients/materials & methods: Urine was collected from control (n = 20), A (n = 31) and NA (n = 23) DMD patients. miRNA expression was measured by reverse transcription-quantitative PCR. RESULTS miR-29c-3p was significantly downregulated in A DMD patients while miR-23b-3p and miR-21-5p were significantly downregulated in NA DMD patients compared with age-matched controls. CONCLUSION miR-29c-3p, miR-23b-3p and miR-21-5p are promising novel noninvasive biomarkers for DMD, and miR-29c-3p levels are differentially affected by different steroid regimens, supporting the antifibrotic effect of steroid therapy.
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Affiliation(s)
- Francesco Catapano
- The Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, 30 Guildford Street, London WC1N 1EH, UK
| | - Joana Domingos
- The Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, 30 Guildford Street, London WC1N 1EH, UK
| | - Mark Perry
- School of Pharmacy & Biomedical Sciences, University of Portsmouth, St Michael's Building, Portsmouth PO1 2DT, UK
| | - Valeria Ricotti
- The Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, 30 Guildford Street, London WC1N 1EH, UK
| | - Lauren Phillips
- John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK
| | - Laurent Servais
- Institute I-Motion, Hôpital Armand Trousseau, Paris 75571-12, France.,Centre de Référence des maladies Neuromusculaires, CHU de Liège, Liège 4000, Belgium
| | - Andreea Seferian
- Institute I-Motion, Hôpital Armand Trousseau, Paris 75571-12, France
| | - Imelda de Groot
- Department of Rehabilitation, Amalia Children's Hospital, Radboud University Medical Centre, Nijmegen 6525 GA, The Netherlands
| | - Yvonne D Krom
- Department of Neurology, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands
| | - Erik H Niks
- Department of Neurology, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands
| | - Jan Jgm Verschuuren
- Department of Neurology, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands
| | - Volker Straub
- Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Institute of Human Genetics, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK
| | - Thomas Voit
- National Institute for Health Research, Great Ormond Street Institute of Child Health Biomedical Research Centre, University College London, London WC1N 1EH, UK
| | - Jennifer Morgan
- The Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, 30 Guildford Street, London WC1N 1EH, UK
| | - Francesco Muntoni
- The Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, 30 Guildford Street, London WC1N 1EH, UK
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Chen Y, Du M, Chen W, Zhu L, Wu C, Zhang Z, Wang M, Chu H, Gu D, Chen J. Polymorphism rs2682818 in miR-618 is associated with colorectal cancer susceptibility in a Han Chinese population. Cancer Med 2018. [PMID: 29533012 PMCID: PMC5911622 DOI: 10.1002/cam4.1409] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
MicroRNAs (miRNAs), endogenous small noncoding RNAs (ncRNAs), play crucial roles in cancer development. Many studies have demonstrated that miRNAs can serve as diagnostic and therapeutic biomarkers for malignancies. Additionally, single nucleotide polymorphisms (SNPs) located in miRNA functional regions have been reported to be involved in cancer susceptibility. In this study, we investigated the associations between SNPs located in miRNA functional regions and colorectal cancer (CRC) susceptibility. We systematically screened all candidate miRNAs and their SNPs and then evaluated the relationships between the SNPs and CRC susceptibility in a Han Chinese population including 878 patients with CRC and 884 controls. Genotyping was performed by TaqMan assay. After comprehensively screening the miRNAs and SNPs, we elected to evaluate the association between SNP rs2682818 in miR‐618 and CRC susceptibility. We found that the AA and AC/AA genotypes of rs2682818 were associated with a decreased risk of CRC compared with the CC genotype (odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.37–0.79 for AA vs. CC in codominant model; OR = 0.82, 95% CI = 0.68–0.99 for AC/AA vs. CC in dominant model). However, we obtained no statically significant results in our subgroup analyses. SNP rs2682818 in miR‐618 has potential as a biomarker for individuals with high CRC susceptibility. Our findings need to be verified in studies including larger samples. Moreover, molecular functional studies of miR‐681 must be performed to confirm its relationship with CRC.
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Affiliation(s)
- Yuetong Chen
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.,Clinical Research Center, Xuyi People's Hospital, Xuyi, Jiangsu, China
| | - Mulong Du
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.,Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Wei Chen
- Department of Digestive Disease, Dongtai Hospital Affiliated to Nantong Medical University, Yancheng, China
| | - Lingjun Zhu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Congye Wu
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Zhengdong Zhang
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Meilin Wang
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Haiyan Chu
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Dongying Gu
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jinfei Chen
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.,Clinical Research Center, Xuyi People's Hospital, Xuyi, Jiangsu, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
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Rapado-González Ó, Majem B, Muinelo-Romay L, Álvarez-Castro A, Santamaría A, Gil-Moreno A, López-López R, Suárez-Cunqueiro MM. Human salivary microRNAs in Cancer. J Cancer 2018; 9:638-649. [PMID: 29556321 PMCID: PMC5858485 DOI: 10.7150/jca.21180] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Accepted: 12/11/2017] [Indexed: 12/25/2022] Open
Abstract
Circulating microRNAs (miRNAs) have emerged as excellent candidates for cancer biomarkers. Several recent studies have highlighted the potential use of saliva for the identification of miRNAs as novel biomarkers, which represents a great opportunity to improve diagnosis and monitor general health and disease. This review summarises the mechanisms of miRNAs deregulation in cancer, the value of targeting them with a therapeutic intention and the evidence of the potential clinical use of miRNAs expressed in saliva for the detection of different cancer types. We also provide a comprehensive review of the different methods for normalising the levels of specific miRNAs present in saliva, as this is a critical step in their analysis, and the challenge to validate salivary miRNAs as a reality to manage cancer patients.
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Affiliation(s)
- Óscar Rapado-González
- Department of Surgery and Medical Surgical Specialties, Medicine and Dentistry School, University of Santiago de Compostela, Spain. Health Research Institute of Santiago (IDIS); Santiago de Compostela, Spain.,Liquid Biopsy Analysis Unit, Translational Medical Oncology, Health Research Institute of Santiago (IDIS), CIBERONC, Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain
| | - Blanca Majem
- Cell Cycle and Cancer Lab, Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Laura Muinelo-Romay
- Liquid Biopsy Analysis Unit, Translational Medical Oncology, Health Research Institute of Santiago (IDIS), CIBERONC, Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain
| | - Ana Álvarez-Castro
- Medical Digestive Service, Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS); Santiago de Compostela, Spain
| | - Anna Santamaría
- Cell Cycle and Cancer Lab, Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Antonio Gil-Moreno
- Cell Cycle and Cancer Lab, Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.,Department of Gynecology Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Rafael López-López
- Liquid Biopsy Analysis Unit, Translational Medical Oncology, Health Research Institute of Santiago (IDIS), CIBERONC, Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain
| | - María Mercedes Suárez-Cunqueiro
- Department of Surgery and Medical Surgical Specialties, Medicine and Dentistry School, University of Santiago de Compostela, Spain. Health Research Institute of Santiago (IDIS); Santiago de Compostela, Spain
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35
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Matboli M, Shafei AE, Shehata HH, Nabil N, Hossam N, Azazy AE, El-Tawdi AH, Abdel-Rahman O. Clinical significance of miRNA-autophagy transcript expression in patients with hepatocellular carcinoma. Biomark Med 2017; 11:641-656. [PMID: 28770611 DOI: 10.2217/bmm-2017-0049] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
AIM This study integrates autophagy transcripts miRNAs expression based on bioinformatic analysis followed by clinical validation. METHODOLOGY Cellular jun proto-oncogene mRNA, LAMP2 mRNA, miR-16 and miR-146a level were investigated in the serum and tissue of patients with hepatocellular carcinoma (HCC), chronic hepatitis C and healthy volunteers by quantitative real-time PCR. The prognostic power of this serum RNA panel was explored. RESULTS The expression of serum cellular jun proto-oncogene mRNA, LAMP2 mRNA, miR-16 and miR-146a were positive in 85.1, 94, 97.1 and 84.2% HCC patients, respectively and they were correlated with tissue levels. Our results suggested that the chosen panel is an independent prognostic factor for survival in patients with HCC. CONCLUSION The current work provides four RNA-based biomarker panel for HCC diagnosis and prognosis.
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Affiliation(s)
- Marwa Matboli
- Oncology Diagnostic Unit, Medical Biochemistry & Molecular biology Department, Faculty of Medicine, Ain Shams University, PO box 11381, Abbassia, Cairo, Egypt
| | - Ayman E Shafei
- Biomedical Research Department, Military Armed Forces College of Medicine
| | - Hanan H Shehata
- Oncology Diagnostic Unit, Medical Biochemistry & Molecular biology Department, Faculty of Medicine, Ain Shams University, PO box 11381, Abbassia, Cairo, Egypt
| | - Nesreen Nabil
- Department of Biochemistry, Faculty of pharmacy, Modern Univesity for Technology & Information, Cairo, Egypt
| | - Nourhan Hossam
- Oncology Diagnostic Unit, Medical Biochemistry & Molecular biology Department, Faculty of Medicine, Ain Shams University, PO box 11381, Abbassia, Cairo, Egypt
| | - Ahmed Em Azazy
- Undergraduate Student, Armed Forces College of Medicine, Cairo, Egypt
| | | | - Omar Abdel-Rahman
- Clinical Oncology Department, Faculty of Medicine, Ain Shams University
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36
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Song XL, Tang Y, Lei XH, Zhao SC, Wu ZQ. miR-618 Inhibits Prostate Cancer Migration and Invasion by Targeting FOXP2. J Cancer 2017; 8:2501-2510. [PMID: 28900488 PMCID: PMC5595080 DOI: 10.7150/jca.17407] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Accepted: 05/28/2017] [Indexed: 01/05/2023] Open
Abstract
miRNAs play critical role in the development and progression of prostate cancer. Here we studied the role of miR-618 in prostate cancer migration and invasion. miR-618 was downregulated in metastatic androgen-independent prostate cancer (AIPC), patients with low miR-618 had poor outcome. Overexpression of miR-618 inhibited migration and invasion and induced mesenchymal to epithelial transition (MET). Conversely, knockdown of miR-618 promoted migration and invasion and induced epithelial to mesenchymal transition (EMT). FOXP2 was the direct target of miR-618, and promoted TGF-β expression, inhibition of TGF-β reversed the effect of miR-618 knockdown. We further analyzed the correlation between miR-618 expression and FOXP2 in human prostate cancer tissues, and found there was a negative correlation between miR-618 expression and FOXP2 levels. In conclusion, we found miR-618 inhibited prostate cancer migration and invasion by targeting FOXP2 and inhibiting TGF-β.
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Affiliation(s)
- Xian-Lu Song
- Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Yao Tang
- Department of Pathology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China.,Guangdong Provincial Key Laboratory of Molecular Oncologic Pathology, Southern Medical University, Guangzhou 510515, China.,Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Xiang-Hui Lei
- Department of Pathology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China.,Guangdong Provincial Key Laboratory of Molecular Oncologic Pathology, Southern Medical University, Guangzhou 510515, China.,Department of Pathology, Affiliated Chenzhou Hospital, Southern Medical University (The First People's Hospital of Chenzhou), Chenzhou 423000, China
| | - Shan-Chao Zhao
- Department of Urology, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
| | - Zi-Qing Wu
- Department of Pathology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China.,Guangdong Provincial Key Laboratory of Molecular Oncologic Pathology, Southern Medical University, Guangzhou 510515, China.,Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
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Circulating miRNAs as novel diagnostic biomarkers in hepatocellular carcinoma detection: a meta-analysis based on 24 articles. Oncotarget 2017; 8:66402-66413. [PMID: 29029522 PMCID: PMC5630422 DOI: 10.18632/oncotarget.18949] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 06/27/2017] [Indexed: 02/07/2023] Open
Abstract
The diagnostic value and suitability of circulating miRNAs for the detection of hepatocellular carcinoma have been inconsistent in the literature. A meta-analysis is used to systematically evaluate the diagnostic value of circulating miRNAs. Eligible studies were selected and the heterogeneity was assessed by subgroup analysis, meta-regression, and publication bias. After strictly and comprehensive screening, the source methods, internal reference and the cut-off values of the included miRNAs were first listed. Circulating miRNAs demonstrated a relatively good diagnostic value in hepatocellular carcinoma, In the subgroup analysis, diagnosis odds ratio showed a higher accuracy with multiple miRNAs than with a single miRNA as well as with serum types than plasma types. In addition, although miRNAs have many expression patterns, the high frequency expression miRNAs (miR-21, miR-199 and miR-122) might be more specific for the diagnosis of hepatocellular carcinoma.The sources of heterogeneity might be related to the number of miRNAs and the specimen types in meta-regression. Furthermore, it’s surprised that the pooled studies were first demonstrated publication bias (P < 0.05). In conclusion, multiple miRNAs in serum have a better diagnostic value, and the publication bias was stable. To validate the potential applicability of miRNAs in the diagnosis of hepatocellular carcinoma, more rigorous studies are needed to confirm these conclusions.
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38
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Elemeery MN, Badr AN, Mohamed MA, Ghareeb DA. Validation of a serum microRNA panel as biomarkers for early diagnosis of hepatocellular carcinoma post-hepatitis C infection in Egyptian patients. World J Gastroenterol 2017; 23:3864-3875. [PMID: 28638226 PMCID: PMC5467072 DOI: 10.3748/wjg.v23.i21.3864] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 01/18/2017] [Accepted: 03/02/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the prospective importance of serum micro (mi)RNAs (miR-125b, miR-138b, miR-1269, miR-214-5p, miR-494, miR375 and miR-145) as early biomarkers for the diagnosis of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).
METHODS Two-hundred and fifty HCV4a patients, 224 HCV4a-HCC patients, and 84 healthy controls were enrolled in the study. Expression levels of miR214-5p, miR-125b, miR-1269 and miR-375 were quantified using quantitative real-time PCR.
RESULTS Expression of the selected miRNAs in serum was significantly lower in HCC patients than in the healthy controls, except for miR-1269 and miR-494. There was a significant difference between HCC and HCV patients, in particular for HCC and late stage fibrosis, rather than HCV patients and early fibrosis. It is obvious that miR-1269 was significantly upregulated in HCC cases compared to hepatic fibrosis cases. Each miRNA can show HCC progression. Multivariate logistic regression analysis indicated that the tested panel of miRNAs (miR214-5p, miR-125b, miR-1269 and miR-375) represent accurate and specific indictors of HCC development.
CONCLUSION This study presents a panel of miRNAs with strong power as putative diagnostic and prognostic biomarkers for HCV-induced HCC. Moreover, miR-214-5p and miR-1269 could be considered as early biomarkers for tracking the progress of liver fibrosis to HCC.
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39
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Gasparri ML, Casorelli A, Bardhi E, Besharat AR, Savone D, Ruscito I, Farooqi AA, Papadia A, Mueller MD, Ferretti E, Benedetti Panici P. Beyond circulating microRNA biomarkers: Urinary microRNAs in ovarian and breast cancer. Tumour Biol 2017; 39:1010428317695525. [PMID: 28459207 DOI: 10.1177/1010428317695525] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Breast cancer is the most common malignancy in women worldwide, and ovarian cancer is the most lethal gynecological malignancy. Women carrying a BRCA1/2 mutation have a very high lifetime risk of developing breast and ovarian cancer. The only effective risk-reducing strategy in BRCA-mutated women is a prophylactic surgery with bilateral mastectomy and bilateral salpingo-oophorectomy. However, many women are reluctant to undergo these prophylactic surgeries due to a consequent mutilated body perception, unfulfilled family planning, and precocious menopause. In these patients, an effective screening strategy is available only for breast cancer, but it only consists in close radiological exams with a significant burden for the health system and a significant distress to the patients. No biomarkers have been shown to effectively detect breast and ovarian cancer at an early stage. MicroRNAs (miRNAs) are key regulatory molecules operating in a post-transcriptional regulation of gene expression. Aberrant expression of miRNAs has been documented in several pathological conditions, including solid tumors, suggesting their involvement in tumorigenesis. miRNAs can be detected in blood and urine and could be used as biomarkers in solid tumors. Encouraging results are emerging in gynecological malignancy as well, and suggest a different pattern of expression of miRNAs in biological fluids of breast and ovarian cancer patients as compared to healthy control. Aim of this study is to highlight the role of the urinary miRNAs which are specifically associated with cancer and to investigate their role in early diagnosis and in determining the prognosis in breast and ovarian cancer.
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Affiliation(s)
- Maria Luisa Gasparri
- 1 Department of Gynecology, Obstetrics and Urology, Sapienza University of Rome, Rome, Italy.,2 Department of Obstetrics and Gynecology, University Hospital of Berne, University of Berne, Berne, Switzerland
| | - Assunta Casorelli
- 1 Department of Gynecology, Obstetrics and Urology, Sapienza University of Rome, Rome, Italy
| | - Erlisa Bardhi
- 1 Department of Gynecology, Obstetrics and Urology, Sapienza University of Rome, Rome, Italy
| | - Aris Raad Besharat
- 1 Department of Gynecology, Obstetrics and Urology, Sapienza University of Rome, Rome, Italy
| | - Delia Savone
- 1 Department of Gynecology, Obstetrics and Urology, Sapienza University of Rome, Rome, Italy
| | - Ilary Ruscito
- 1 Department of Gynecology, Obstetrics and Urology, Sapienza University of Rome, Rome, Italy
| | - Ammad Ahmad Farooqi
- 3 Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan
| | - Andrea Papadia
- 2 Department of Obstetrics and Gynecology, University Hospital of Berne, University of Berne, Berne, Switzerland
| | - Michael David Mueller
- 2 Department of Obstetrics and Gynecology, University Hospital of Berne, University of Berne, Berne, Switzerland
| | - Elisabetta Ferretti
- 4 Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.,5 Neuromed Institute, Pozzilli, Italy
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Zhu HT, Liu RB, Liang YY, Hasan AME, Wang HY, Shao Q, Zhang ZC, Wang J, He CY, Wang F, Shao JY. Serum microRNA profiles as diagnostic biomarkers for HBV-positive hepatocellular carcinoma. Liver Int 2017; 37:888-896. [PMID: 28061012 DOI: 10.1111/liv.13356] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2016] [Revised: 12/30/2016] [Accepted: 12/31/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS The discovery of effective and reliable biomarkers to detect hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC) at an early stage may improve the survival of HCC. The aim of this study was to establish serum microRNA (miRNA) profiles as diagnostic biomarkers for HBV-positive HCC. METHODS We used deep sequencing to screen serum miRNAs in a discovery cohort (n=100). Quantitative polymerase chain reaction (qPCR) assays were then applied to evaluate the expression of selected miRNAs. A diagnostic 2-miRNA panel was established by a logistic regression model using a training cohort (n=182). The predicted probability of being detected as HCC was used to construct the receiver operating characteristic (ROC) curve. Area under the ROC curve (AUC) was used to assess the diagnostic performance of the selected miRNA panel. RESULTS The predicted probability of being detected as HCC by the 2-miRNA panel was calculated by: logit P=-2.988 + 1.299 × miR-27b-3p + 1.245 × miR-192-5p. These results were further confirmed in a validation cohort (n=246).The miRNA panel provided a high diagnostic accuracy of HCC (AUC=0.842, P<.0001 for training set; AUC=0.836, P<.0001 for validation set respectively). In addition, the miRNA panel showed better prediction of HCC diagnosis than did alpha-foetoprotein (AFP). The miRNA panel also differentiated HCC from healthy (AUC=0.823, P<.0001), and cirrhosis patients (AUC=0.859, P<.0001) respectively. CONCLUSIONS Differentially expressed serum miRNAs may have considerable clinical value in HCC diagnosis, and be particularly helpful for AFP-negative HCC.
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Affiliation(s)
- Hao-Tu Zhu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Rong-Bin Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ya-Yong Liang
- Department of paediatrics, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Abdulbaqi M E Hasan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Hai-Yun Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Qiong Shao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zi-Chen Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jing Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Cai-Yun He
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Fang Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jian-Yong Shao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
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Bradshaw G, Sutherland HG, Haupt LM, Griffiths LR. Dysregulated MicroRNA Expression Profiles and Potential Cellular, Circulating and Polymorphic Biomarkers in Non-Hodgkin Lymphoma. Genes (Basel) 2016; 7:genes7120130. [PMID: 27999330 PMCID: PMC5192506 DOI: 10.3390/genes7120130] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Revised: 11/23/2016] [Accepted: 12/05/2016] [Indexed: 02/07/2023] Open
Abstract
A large number of studies have focused on identifying molecular biomarkers, including microRNAs (miRNAs) to aid in the diagnosis and prognosis of the most common subtypes of non-Hodgkin lymphoma (NHL), Diffuse Large B-cell Lymphoma and Follicular Lymphoma. NHL is difficult to diagnose and treat with many cases becoming resistant to chemotherapy, hence the need to identify improved biomarkers to aid in both diagnosis and treatment modalities. This review summarises more recent research on the dysregulated miRNA expression profiles found in NHL, as well as the regulatory role and biomarker potential of cellular and circulating miRNAs found in tissue and serum, respectively. In addition, the emerging field of research focusing on miRNA single nucleotide polymorphisms (miRSNPs) in genes of the miRNA biogenesis pathway, in miRNA genes themselves, and in their target sites may provide new insights on gene expression changes in these genes. These miRSNPs may impact miRNA networks and have been shown to play a role in a host of different cancer types including haematological malignancies. With respect to NHL, a number of SNPs in miRNA-binding sites in target genes have been shown to be associated with overall survival.
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Affiliation(s)
- Gabrielle Bradshaw
- Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia.
| | - Heidi G Sutherland
- Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia.
| | - Larisa M Haupt
- Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia.
| | - Lyn R Griffiths
- Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia.
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42
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Roest HP, Verhoeven CJ, de Haan JE, de Jonge J, IJzermans JN, van der Laan LJ. Improving Accuracy of Urinary miRNA Quantification in Heparinized Patients Using Heparinase I Digestion. J Mol Diagn 2016; 18:825-833. [DOI: 10.1016/j.jmoldx.2016.06.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Revised: 05/31/2016] [Accepted: 06/16/2016] [Indexed: 10/21/2022] Open
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43
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He S, Hu XW, Wang D, Han LF, Zhang DC, Wei C. Accuracy of microRNAs for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2016; 40:405-17. [PMID: 27016891 DOI: 10.1016/j.clinre.2016.02.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Revised: 02/01/2016] [Accepted: 02/17/2016] [Indexed: 02/04/2023]
Abstract
Due to the high morbidity, mortality and late detection of hepatocellular carcinoma (HCC), it becomes a major public health challenge. MicroRNAs (miRNAs) have been reported to be aberrantly expressed in patients with HCC and thus may serve as potential diagnostic biomarkers. The aim of this study was to systematically assess the diagnostic accuracy of miRNAs as biomarkers for diagnosing HCC through a meta-analysis. Our results indicated that serum miRNAs had a relatively high diagnostic value for HCC diagnosis; the combination of serum α-fetoprotein (AFP) and miRNAs displayed a better diagnostic accuracy than using AFP or miRNAs alone; the combination of multiple miRNAs assay in serum had the highest diagnostic accuracy in HCC diagnosis based on the published data. In conclusion, our meta-analysis suggests that miRNAs, especially serum miRNAs, had a relatively high diagnostic value for HCC diagnosis, which can discriminate HCC from healthy subjects and those with chronic hepatitis and cirrhosis easily, and may serve as a novel, less-invasive screening tool.
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Affiliation(s)
- Song He
- Maanshan Center for Clinical Laboratory, Maanshan Municipal Hospital Group, 45, Hubei Road, Maanshan 243000, China.
| | - Xiao-Wu Hu
- Maanshan Center for Clinical Laboratory, Maanshan Municipal Hospital Group, 45, Hubei Road, Maanshan 243000, China
| | - Dong Wang
- Maanshan Center for Clinical Laboratory, Maanshan Municipal Hospital Group, 45, Hubei Road, Maanshan 243000, China
| | - Ling-Fei Han
- Maanshan Center for Clinical Laboratory, Maanshan Municipal Hospital Group, 45, Hubei Road, Maanshan 243000, China
| | - De-Chun Zhang
- Molecular Medicine & Tumor Research Center, Chongqing Medical University, Chongqing 400016, China
| | - Cheng Wei
- Maanshan Center for Clinical Laboratory, Maanshan Municipal Hospital Group, 45, Hubei Road, Maanshan 243000, China
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Morales S, Gulppi F, Gonzalez-Hormazabal P, Fernandez-Ramires R, Bravo T, Reyes JM, Gomez F, Waugh E, Jara L. Association of single nucleotide polymorphisms in Pre-miR-27a, Pre-miR-196a2, Pre-miR-423, miR-608 and Pre-miR-618 with breast cancer susceptibility in a South American population. BMC Genet 2016; 17:109. [PMID: 27421647 PMCID: PMC4946190 DOI: 10.1186/s12863-016-0415-0] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2016] [Accepted: 07/08/2016] [Indexed: 02/07/2023] Open
Abstract
Background MicroRNAs (miRNAs) are a novel class of endogenous, non-coding, single-stranded RNAs capable of regulating gene expression by suppressing translation or degrading mRNAs. Single nucleotide polymorphisms (SNP) can alter miRNA expression, resulting in diverse functional consequences. Previous studies have examined the association of miRNA SNPs with breast cancer (BC) susceptibility. The contribution of miRNA gene variants to BC susceptibility in South American women had been unexplored. Our study evaluated the association of the SNPs rs895819 in pre-miR27a, rs11614913 in pre-miR-196a2, rs6505162 in pre-miR-423, rs4919510 in miR-608, and rs2682818 in pre-mir-618 with familial BC and early-onset non-familial BC in non-carriers of BRCA1/2 mutations from a South American population. Results We evaluated the association of five SNPs with BC risk in 440 cases and 807 controls. Our data do not support an association of rs11614913:C > T and rs4919510:C > G with BC risk. The rs6505162:C > A was significantly associated with increased risk of familial BC in persons with a strong family history of BC (OR = 1.7 [95 % CI 1.0–2.0] p = 0.05). The rs2682818:C > A genotype C/A is associated with an increased BC risk in non-familial early-onset BC. For the rs895819:A > G polymorphism, the genotype G/G is significantly associated with reduced BC risk in families with a moderate history of BC (OR = 0.3 [95 % CI 0.1–0.8] p = 0.01). Conclusions The contribution of variant miRNA genes to BC in South American women had been unexplored. Our findings support the following conclusions: a) rs6505162:C > A in pre-miR-423 increases risk of familial BC in families with a strong history of BC; b) the C/A genotype at rs2682818:C > A (pre-miR-618) increases BC risk in non-familial early-onset BC; and c) the G/G genotype at rs895819:A > G (miR-27a) reduces BC risk in families with a moderate history of BC.
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Affiliation(s)
- Sebastián Morales
- Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile.,Universidad Andres Bello, Facultad de Ciencias Biológicas, República N°217, Santiago, Chile
| | - Felipe Gulppi
- Hospital Clínico San Borja Arriaran, Avenida Santa Rosa 1234, Santiago, Chile
| | - Patricio Gonzalez-Hormazabal
- Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile
| | - Ricardo Fernandez-Ramires
- Pathology and Oral Medicine, School of Odontology, University of Chile, Sergio Livingstone Pohlhammer 943, Santiago, Chile
| | - Teresa Bravo
- National Cancer Society Corporación Nacional del Cáncer CONAC, Santiago, Chile
| | | | | | | | - Lilian Jara
- Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. .,Laboratorio de Genética Molecular Humana, Facultad de Medicina, Instituto de Ciencias Biomédicas (ICBM), Programa de Genética, Universidad de Chile, Independencia 1027, Santiago, Chile.
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45
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Larrea E, Sole C, Manterola L, Goicoechea I, Armesto M, Arestin M, Caffarel MM, Araujo AM, Araiz M, Fernandez-Mercado M, Lawrie CH. New Concepts in Cancer Biomarkers: Circulating miRNAs in Liquid Biopsies. Int J Mol Sci 2016; 17:ijms17050627. [PMID: 27128908 PMCID: PMC4881453 DOI: 10.3390/ijms17050627] [Citation(s) in RCA: 181] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2016] [Revised: 04/18/2016] [Accepted: 04/18/2016] [Indexed: 12/19/2022] Open
Abstract
The effective and efficient management of cancer patients relies upon early diagnosis and/or the monitoring of treatment, something that is often difficult to achieve using standard tissue biopsy techniques. Biological fluids such as blood hold great possibilities as a source of non-invasive cancer biomarkers that can act as surrogate markers to biopsy-based sampling. The non-invasive nature of these “liquid biopsies” ultimately means that cancer detection may be earlier and that the ability to monitor disease progression and/or treatment response represents a paradigm shift in the treatment of cancer patients. Below, we review one of the most promising classes of circulating cancer biomarkers: microRNAs (miRNAs). In particular, we will consider their history, the controversy surrounding their origin and biology, and, most importantly, the hurdles that remain to be overcome if they are really to become part of future clinical practice.
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Affiliation(s)
- Erika Larrea
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - Carla Sole
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - Lorea Manterola
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - Ibai Goicoechea
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - María Armesto
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - María Arestin
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - María M Caffarel
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
- IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain.
| | - Angela M Araujo
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - María Araiz
- Hematology Department, Donostia Hospital, 20014 San Sebastián, Spain.
| | | | - Charles H Lawrie
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
- IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain.
- Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9DU, UK.
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46
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Wang Y, Tian Y. miRNA for diagnosis and clinical implications of human hepatocellular carcinoma. Hepatol Res 2016; 46:89-99. [PMID: 26284466 DOI: 10.1111/hepr.12571] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Revised: 06/12/2015] [Accepted: 08/10/2015] [Indexed: 12/14/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies, as a result of being asymptomatic at early stage, subsequent late clinical confirmation and poor prognosis. It is urgent to search more accurate biomarkers for diagnosing early HCC and predicting prognosis. Many factors participate in liver carcinogenesis, including dysregulation of miRNA. miRNA were endogenously expressed non-coding single-stranded small RNA with 19-25 nucleotides. Accumulating evidences have showed that miRNA from circulation and solitary tumors may be useful to classify the differentiation degree and stages of HCC, detect the hepatitis B/C virus-related HCC, and predict the survival rate after surgical resection or orthotopic liver transplantation. In this review, we summarize dysregulated miRNA, their roles in diagnosis and clinical implications of HCC.
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Affiliation(s)
- Yurong Wang
- Core Laboratory of Translational Medicine, Chinese PLA General Hospital, Beijing, China.,School of Medicine, Nankai University, Tianjin, China
| | - Yaping Tian
- Core Laboratory of Translational Medicine, Chinese PLA General Hospital, Beijing, China.,School of Medicine, Nankai University, Tianjin, China
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47
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Pichulik T, Khatamzas E, Liu X, Brain O, Delmiro Garcia M, Leslie A, Danis B, Mayer A, Baban D, Ragoussis J, Weber ANR, Simmons A. Pattern recognition receptor mediated downregulation of microRNA-650 fine-tunes MxA expression in dendritic cells infected with influenza A virus. Eur J Immunol 2016; 46:167-77. [PMID: 26460926 PMCID: PMC4738369 DOI: 10.1002/eji.201444970] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Revised: 09/14/2015] [Accepted: 10/02/2015] [Indexed: 12/11/2022]
Abstract
MicroRNAs are important posttranscriptional regulators of gene expression, which have been shown to fine-tune innate immune responses downstream of pattern recognition receptor (PRR) signaling. This study identifies miR-650 as a novel PRR-responsive microRNA that is downregulated upon stimulation of primary human monocyte-derived dendritic cells (MDDCs) with a variety of different microbe-associated molecular patterns. A comprehensive target search combining in silico analysis, transcriptional profiling, and reporter assays reveals that miR-650 regulates several well-known interferon-stimulated genes, including IFIT2 and MXA. In particular, downregulation of miR-650 in influenza A infected MDDCs enhances the expression of MxA and may therefore contribute to the establishment of an antiviral state. Together these findings reveal a novel link between miR-650 and the innate immune response in human MDDCs.
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Affiliation(s)
- Tica Pichulik
- MRC Human Immunology UnitWeatherall Institute of Molecular MedicineJohn Radcliffe HospitalHeadingtonOxfordUK
- Department of ImmunologyInterfaculty Institute for Cell BiologyUniversity of TübingenTübingenGermany
| | - Elham Khatamzas
- MRC Human Immunology UnitWeatherall Institute of Molecular MedicineJohn Radcliffe HospitalHeadingtonOxfordUK
| | - Xiao Liu
- Department of ImmunologyInterfaculty Institute for Cell BiologyUniversity of TübingenTübingenGermany
| | - Oliver Brain
- MRC Human Immunology UnitWeatherall Institute of Molecular MedicineJohn Radcliffe HospitalHeadingtonOxfordUK
- Translational Gastroenterology UnitJohn Radcliffe HospitalHeadingtonOxfordUK
| | - Magno Delmiro Garcia
- Department of ImmunologyInterfaculty Institute for Cell BiologyUniversity of TübingenTübingenGermany
| | - Alasdair Leslie
- MRC Human Immunology UnitWeatherall Institute of Molecular MedicineJohn Radcliffe HospitalHeadingtonOxfordUK
| | - Benedicte Danis
- MRC Human Immunology UnitWeatherall Institute of Molecular MedicineJohn Radcliffe HospitalHeadingtonOxfordUK
| | - Alice Mayer
- MRC Human Immunology UnitWeatherall Institute of Molecular MedicineJohn Radcliffe HospitalHeadingtonOxfordUK
| | - Dilair Baban
- Wellcome Trust Centre for Human GeneticsOxfordUK
| | | | - Alexander N. R. Weber
- Department of ImmunologyInterfaculty Institute for Cell BiologyUniversity of TübingenTübingenGermany
| | - Alison Simmons
- MRC Human Immunology UnitWeatherall Institute of Molecular MedicineJohn Radcliffe HospitalHeadingtonOxfordUK
- Translational Gastroenterology UnitJohn Radcliffe HospitalHeadingtonOxfordUK
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48
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Tan Y, Ge G, Pan T, Wen D, Gan J. Serum MiRNA panel as potential biomarkers for chronic hepatitis B with persistently normal alanine aminotransferase. Clin Chim Acta 2015; 451:232-9. [PMID: 26483130 DOI: 10.1016/j.cca.2015.10.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2014] [Revised: 09/25/2015] [Accepted: 10/02/2015] [Indexed: 02/09/2023]
Abstract
BACKGROUND Circulating miRNAs, a family of miRNAs existing in plasma and serum, have a great potential to serve as novel biomarkers in body fluids for non-invasive diagnosis and prognosis of many diseases. METHODS A multistage, case-control study was designed to establish a panel of serum miRNAs that could be surrogate markers for chronic hepatitis B with persistently normal alanine aminotransferase (ALT). A total of 295 CHB patients presenting persistently normal ALT levels with significant histological features (SPNALT group), 243 CHB patients presenting persistently normal ALT levels with no significant histological features (NSPNALT group), and 178 healthy controls (healthy group) were enrolled in the study. An initial screening of miRNAs was performed by Illumina sequencing using serum samples pooled from SPNALT patients and controls. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assay was performed to evaluate the expression of selected miRNAs. A logistic regression model was constructed using a training cohort (n=380) and validated using a cohort (n=258). The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. RESULTS We identified 9 miRNAs (hsa-miR-885-5p, hsa-miR-122-5p, hsa-miR-10a-5p, hsa-miR-511-5p, hsa-miR-574-5p, hsa-miR-98-5p, hsa-miR-26a-5p, hsa-miR-192-5p, hsa-miR-30b-5p) and established 3 miRNA panels that provided high diagnostic accuracy for SPNALT. The AUC of miRNA panels for SPNALT vs. healthy was 0.882 (95% CI=0.839 to 0.925), for SPNALT vs. NSPNALT was 0.894 (95% CI=0.857 to 0.930), and for SPNALT vs. control was 0.860 (95% CI=0.821 to 0.899). CONCLUSIONS We constructed serum miRNA panels with considerable clinical value in diagnosing PNALT.
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Affiliation(s)
- Youwen Tan
- Department of Hepatosis, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, China.
| | - Guohong Ge
- Department of Hepatosis, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, China
| | - Tengli Pan
- Department of Hepatosis, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, China
| | - Danfeng Wen
- Department of Hepatosis, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, China
| | - Jianhe Gan
- Department of Hepatosis, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, China
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49
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Debernardi S, Massat NJ, Radon TP, Sangaralingam A, Banissi A, Ennis DP, Dowe T, Chelala C, Pereira SP, Kocher HM, Young BD, Bond-Smith G, Hutchins R, Crnogorac-Jurcevic T. Noninvasive urinary miRNA biomarkers for early detection of pancreatic adenocarcinoma. Am J Cancer Res 2015; 5:3455-3466. [PMID: 26807325 PMCID: PMC4697691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 09/15/2015] [Indexed: 06/05/2023] Open
Abstract
Currently, the majority of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) present with locally invasive and/or metastatic disease, resulting in five-year survival of less than 5%. The development of an early diagnostic test is, therefore, expected to significantly impact the patient's prognosis. In this study, we successfully evaluated the feasibility of identifying diagnostic cell free microRNAs (miRNAs) for early stage PDAC, through the analysis of urine samples. Using Affymetrix microarrays, we established a global miRNA profile of 13 PDAC, six chronic pancreatitis (CP), and seven healthy (H) urine specimens. Selected differentially expressed miRNAs were subsequently investigated using an independent technique (RT-PCR) on 101 urine samples including 46 PDAC, 29 CP and 26 H. Receiver operating characteristic (ROC) and logistic regression analyses were applied to determine the discriminatory potential of the candidate miRNA biomarkers. Three miRNAs (miR-143, miR-223, and miR-30e) were significantly over-expressed in patients with Stage I cancer when compared with age-matched healthy individuals (P=0.022, 0.035 and 0.04, respectively); miR-143, miR-223 and miR-204 were also shown to be expressed at higher levels in Stage I compared to Stages II-IV PDAC (P=0.025, 0.013 and 0.008, respectively). Furthermore, miR-223 and miR-204 were able to distinguish patients with early stage cancer from patients with CP (P=0.037 and 0.036). Among the three biomarkers, miR-143 was best able to differentiate Stage I (n=6) from healthy (n=26) with area under the curve (AUC) of 0.862 (95% CI 0.695-1.000), with sensitivity (SN) of 83.3% (95% CI 50.0-100.0), and specificity (SP) of 88.5% (95% CI 73.1-100.0). The combination of miR-143 with miR-30e was significantly better at discriminating between these two groups, achieving an AUC of 0.923 (95% CI 0.793-1.000), with SN of 83.3% (95% CI 50.0-100.0) and SP of 96.2% (95% CI 88.5-100.0). In this feasibility study, we demonstrate for the first time the utility of miRNA biomarkers for non-invasive, early detection of PDAC in urine specimens.
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Affiliation(s)
- Silvana Debernardi
- Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of LondonLondon, UK
| | - Nathalie J Massat
- Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of LondonLondon, UK
| | - Tomasz P Radon
- Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of LondonLondon, UK
| | - Ajanthah Sangaralingam
- Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of LondonLondon, UK
| | - Ana Banissi
- Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of LondonLondon, UK
| | - Darren P Ennis
- Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of LondonLondon, UK
| | - Thomas Dowe
- Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of LondonLondon, UK
| | - Claude Chelala
- Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of LondonLondon, UK
| | - Stephen P Pereira
- Institute for Liver and Digestive Health, University College LondonLondon, UK
| | - Hemant M Kocher
- Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of LondonLondon, UK
- Barts and The London HPB Centre, Barts Health NHS Trust, Royal London HospitalLondon, UK
| | - Bryan D Young
- Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of LondonLondon, UK
| | - Giles Bond-Smith
- Barts and The London HPB Centre, Barts Health NHS Trust, Royal London HospitalLondon, UK
| | - Robert Hutchins
- Barts and The London HPB Centre, Barts Health NHS Trust, Royal London HospitalLondon, UK
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50
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Huang JT, Liu SM, Ma H, Yang Y, Zhang X, Sun H, Zhang X, Xu J, Wang J. Systematic Review and Meta-Analysis: Circulating miRNAs for Diagnosis of Hepatocellular Carcinoma. J Cell Physiol 2015; 231:328-35. [PMID: 26291451 DOI: 10.1002/jcp.25135] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Accepted: 08/14/2015] [Indexed: 12/17/2022]
Abstract
Because early-stage hepatocellular carcinoma (HCC) is difficult to diagnose using the existing techniques, identifying better biomarkers would likely improve the patients' prognoses. We performed a systematic review and meta-analysis of published studies to appraise the utility of microRNAs (miRNAs) for the early diagnosis of HCC. Pertinent literature was collected from the Medline, Embase, and Chinese National Knowledge Infrastructure databases. We analyzed 50 studies that included 3423 cases of HCC, 2403 chronic hepatic disease (CH) patients, and 1887 healthy controls in 16 articles. Summary receiver operating characteristic analyses of all miRNAs showed an area under the curve (AUC) of 0.82, with 75.8% sensitivity and 75.0% specificity in discriminating patients with HCC from healthy controls. miR-21 and miR-122 individually distinguished patients with HCC from healthy controls, with an AUC of 0.88 for miR-21 and 0.77 for miR-122. The sensitivity and specificity for miR-21 were 86.6% and 79.5%, respectively, those for miR-122 were 68.0% and 73.3%. We conclude that circulating miRNAs, particularly miR-21, and miR-122, are promising biomarkers for the early diagnosis of HCC.
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Affiliation(s)
- Jing-Tao Huang
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P. R. China
| | - Song-Mei Liu
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P. R. China
| | - Haiqing Ma
- Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, P. R. China
| | - Ying Yang
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P. R. China
| | - Xuan Zhang
- Scientific Research Center, Shanghai Public Health Clinical Center, Shanghai, Jinshan District, P. R. China
| | - Huanhuan Sun
- Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, P. R. China
| | - Xiaoyan Zhang
- Scientific Research Center, Shanghai Public Health Clinical Center, Shanghai, Jinshan District, P. R. China
| | - Jianqing Xu
- Scientific Research Center, Shanghai Public Health Clinical Center, Shanghai, Jinshan District, P. R. China
| | - Jin Wang
- Scientific Research Center, Shanghai Public Health Clinical Center, Shanghai, Jinshan District, P. R. China.,Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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