Dataset Information

Circulating microRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is the fifth most common cancer with high mortality, due to late diagnosis and limited treatment options. Blood miRNAs, which circulate in a highly stable, cell-free form, show promise as novel potential biomarkers for early detection of HCC. Whole miRNome profiling was performed to identify deregulated miRNAs between HCC and normal healthy (NH) volunteers. These deregulated miRNAs were validated in an independent cohort of HCC, NH and chronic Hepatitis B (CHB) volunteers and finally in a 3^rd cohort comprising NH, CHB, cirrhotic and HCC volunteers to evaluate miRNA changes during disease progression. The associations between circulating miRNAs and liver-damage markers, clinicopathological characteristics and survival outcomes were analysed to identify prognostic markers. Twelve miRNAs are differentially expressed between HCC and NH individuals in all three cohorts. Five upregulated miRNAs (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p and miR-148a-3p) in CHB, cirrhosis and HCC patients are potential biomarkers for CHB infection, while miR-34a-5p can be a biomarker for cirrhosis. Notably, four miRNAs (miR-1972, miR-193a-5p, miR-214-3p and miR-365a-3p) can distinguish HCC from other non-HCC individuals. Six miRNAs are potential prognostic markers for overall survival.

SUBMITTER: Jin Y

PROVIDER: S-EPMC6639394 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Circulating microRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma.

Jin Yu Y Wong Ye Shen YS Goh Brian K P BKP Chan Chung Yip CY Cheow Peng Chung PC Chow Pierce K H PKH Lim Tony K H TKH Goh George B B GBB Krishnamoorthy Thinesh Lee TL Kumar Rajneesh R Ng Tze Pin TP Chong Samuel S SS Tan Hwee Huang HH Chung Alexander Y F AYF Ooi London Lucien P J LLPJ Chang Jason P E JPE Tan Chee Kiat CK Lee Caroline G L CGL

Scientific reports 20190718 1

Hepatocellular carcinoma (HCC) is the fifth most common cancer with high mortality, due to late diagnosis and limited treatment options. Blood miRNAs, which circulate in a highly stable, cell-free form, show promise as novel potential biomarkers for early detection of HCC. Whole miRNome profiling was performed to identify deregulated miRNAs between HCC and normal healthy (NH) volunteers. These deregulated miRNAs were validated in an independent cohort of HCC, NH and chronic Hepatitis B (CHB) vol ...[more]

PMID: 31320713

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Project description:ObjectiveDiabetic retinopathy (DR) is a common diabetic microvascular complication and a major cause of acquired vision loss. Finding effective biomarkers for the early identification and diagnosis of DR is crucial. This study aimed to comprehensively evaluate the accuracy of microRNAs (miRNAs) in the diagnosis of DR via a meta-analysis of previously published diagnostic studies. This study has been registered on the PROSPERO website, with the number CRD42022323238.MethodsWe searched PubMed, Cochrane Library, Embase, Web of Science, China Wanfang database, and China Knowledge Network database to identify relevant articles published from the time of database creation to April 10, 2022. Stata 14.0 software was used to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), and area under the summary receiver operating characteristic (ROC) curve to assess the accuracy of miRNAs in the diagnosis of DR. Heterogeneity between studies was assessed using Cochran-Q test and I2 statistic for quantitative analysis. The random-effect model was selected due to significant heterogeneity. Subgroup analysis and regression analysis were also performed to determine the potential sources of heterogeneity.ResultsWe included 25 articles detailing 52 studies with 1987 patients with DR and 1771 non-DR controls. The findings demonstrated overall sensitivity (0.82, 95% CI: 0.78 ~ 0.85), specificity (0.84, 95% CI: 0.81 ~ 0.86), PLR (5.0, 95% CI: 4.2 ~ 5.9), NLR (0.22, 95% CI: 0.18 ~ 0.26), and the area under the summary ROC curve (0.90, 95% CI: 0.87 ~ 0.92). Furthermore, we performed subgroup analysis and found that panels of multiple miRNAs could enhance the pooled sensitivity (sensitivity, specificity, and AUC values were 0.89, 0.87, and 0.94, respectively).ConclusionThe meta-analysis showed that miRNAs can be used as potential diagnostic markers for DR, with high accuracy of diagnoses observed with the detection of miRNAs in plasma and serum.

Project description:BackgroundHepatocellular carcinoma (HCC) most commonly develops in patients who have a viral infection, especially in the case of hepatitis B virus (HBV), and in patients with a chronic liver disease. HCC patients with bone metastasis (BM) suffer from pain and other symptoms that significantly reduce their quality of life. Identification of patients who are at high risk for BM after undergoing potentially curative treatment for HCC remains challenging. Here, we aimed to identify HCC BM-related genes and proteins to establish prediction biomarkers.MethodsRNA was extracted from 48 pairs of intratumoral and peritumoral formalin-fixed, paraffin-embedded tissue from HCC patients with and without BM. A cDNA-mediated annealing, selection, extension and ligation assay containing 502 cancer-related genes was used to identify novel BM-associated genes. An additional independent study with 350 HCC patients who had undergone hepatectomy was conducted to evaluate the expression of candidate genes at the protein level using immunohistochemistry on tissue microarrays (TMAs). Of the 350 patients, 273 (78.0%) were infected with HBV.ResultsSeven intratumoral genes and 17 peritumoral genes were overexpressed in patients with BM, whereas 15 intratumoral genes and 28 peritumoral genes were underexpressed in patients with BM. We selected the following four genes for further analysis because they were differentially expressed in the cancer gene-specific microarray and were previously reported to be associated with BM: connective tissue growth factor (CTGF), matrix metalloproteinase-1 (MMP-1), transforming growth factor β1 (TGF-β1), and interleukin-11 (IL-11). We assessed the protein expression of these selected genes using immunohistochemistry on TMAs including 350 HCC patient specimens. We determined that expression of intratumoral CTGF, intratumoral IL-11, and peritumoral MMP-1 were independent prognostic factors for developing BM in HCC patients. Combining intratumoral CTGF and IL-11 expression was also an independent risk factor for BM development.ConclusionsSixty-seven genes were differentially expressed in HCC patients with and without BM. High intratumoral CTGF, positive IL-11, and high peritumoral MMP-1 expression were associated with BM after hepatectomy. Intratumoral CTGF expression combined with IL-11 expression may serve as a useful predictive biomarker for HCC BM.

Dataset Information

Circulating microRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma.

Publications

Circulating microRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma.

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