Dataset Information

Circulating plasma exosomal miRNA profiles serve as potential metastasis-related biomarkers for hepatocellular carcinoma.

ABSTRACT: Exosomes carry functional molecules that can regulate cancer progression. Understanding the function of exosomal markers may provide invaluable insights into the mechanism of metastasis in hepatocellular carcinoma (HCC). The aim of the present study was to identify metastasis-associated microRNAs (miRNAs/miRs) expressed in plasma exosomes. A miRNA microarray and reverse transcription-quantitative PCR were used to analyze the plasma exosome miRNA expression profiles of patients with metastatic or non-metastatic HCC. Receiver operating characteristic (ROC) curve and Kaplan-Meier analyses were used to evaluate the predictive performance and prognostic efficacy of candidate miRNAs identified in the Gene Expression Omnibus database (dataset accession no. GSE67140). Bioinformatics analysis was used to examine the role of exosomal miRNAs in HCC metastasis. A total of 32 miRNAs were differentially expressed in plasma exosomes of patients with metastatic HCC compared with in those of patients with non-metastatic HCC. Additionally, the expression levels of six miRNAs were consistent between plasma exosome samples and matched tissue samples. ROC analysis demonstrated that miR-18a, miR-27a and miR-20b could discriminate metastatic HCC from non-metastatic HCC. Furthermore, the prognostic efficacy of the combination of three miRNAs (miR-18a, miR-20b and miR-221) was superior to that of individual miRNAs. Survival analysis demonstrated that high expression levels of the candidate miRNAs were associated with poor prognosis. Bioinformatics analysis indicated that the potential target genes of these miRNAs were involved in biological processes, molecular functions and cellular components that were associated with metastasis. The present findings suggested that these exosomal miRNAs may serve important roles in HCC lung metastasis and could represent a complementary clinical tool for the assessment of HCC prognosis.

SUBMITTER: Huang C

PROVIDER: S-EPMC7798106 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circulating plasma exosomal miRNA profiles serve as potential metastasis-related biomarkers for hepatocellular carcinoma.

Huang Chunyu C Tang Shuiying S Shen Dong D Li Xiangzhao X Liang Li L Ding Yanqing Y Xu Bihong B

Oncology letters 20210104 2

Exosomes carry functional molecules that can regulate cancer progression. Understanding the function of exosomal markers may provide invaluable insights into the mechanism of metastasis in hepatocellular carcinoma (HCC). The aim of the present study was to identify metastasis-associated microRNAs (miRNAs/miRs) expressed in plasma exosomes. A miRNA microarray and reverse transcription-quantitative PCR were used to analyze the plasma exosome miRNA expression profiles of patients with metastatic or ...[more]

PMID: 33552286

Similar Datasets

Project description:This study evaluated differences in the clinical appearance of patients with hepatocellular carcinoma (HCC) based on plasma level and regulation of microRNAs (miRNA-29c, miRNA-21, and miRNA-155). The observational-analytical study with a cross-sectional design was conducted on 36 HCC patients and 36 healthy controls. The blood samples were collected from 2 Province Hospitals (Dr. Sardjito Hospital and Prof. Dr. Margono Soekarjo Hospital) for HCC and the Blood Bank Donor of the Indonesian Red Cross for 36 healthy controls. These blood samples were treated as follows: plasma isolation, RNA isolation, cDNA synthesis, quantification by qRT-PCR using a sequence-specific forward primer, and normalization of miRNA using housekeeping-stably miRNA-16. There were only 27 HCC patients with complete clinical variables (neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), platelet count, albumin, C-reactive protein (CRP), and cholinesterase (ChE)) that were able to analyses for regulation miRNAs based on its fold change expression miRNA target. All 27 HCC subjects were follow-up until 3-years of monitoring for their overall survival. The miRNA plasma expression was analyzed by Bio-Rad CFX 96 Manager software to determine the cycle of quantification, followed by the calculation of expression levels using Livak's methods. Data were analyzed using STATA 11.0, with a significant value of p<0.05. The miRNAs expression of HCC subjects were lower than that healthy control subjects in miRNA-29c (down-regulation 1.83-fold), higher than that healthy control subjects in miRNA 21 and miRNA-155 (up-regulation, 1.74-fold; 1.55-fold) respectively. NLR, CRP, ChE, and platelet count showed a significant difference in miRNA-29c regulation, though neutrophil count showed a significant difference in miRNA-21 and miRNA-155 regulation (p<0.05). Conclusion: Plasma biomarkers: miRNA-21 and miRNA-155 might be potential biomarkers as onco-miR in HCC subjects, while miRNA-29c might act as a tumor suppressor. Significant evidence was identified with clinical progression based on the regulation of miRNAs, which was consistent with miRNA -29c.

Project description:Background: Chemotherapy is one of the most common therapies used in the treatment of colorectal cancer (CRC), but chemoresistance inevitably occurs. It is challenging to obtain an immediate and accurate diagnosis of chemoresistance. The potential of circulating exosomal miRNAs as oxaliplatin-based chemoresistant biomarkers in CRC patients was investigated in this study. Methods: Plasma exosomal miRNAs in sensitive and resistant patients were analyzed by miRNA microarray analysis, followed by verification with a quantitative reverse-transcription polymerase chain reaction (RT-qPCR) assay in two independent cohorts. The diagnostic accuracy was determined by ROC curve analysis. Logistic regression analysis and Spearman's rank correlation test were also performed. Finally, bioinformatics was used to preliminarily explore the potential molecular mechanism of the selected miRNAs in chemoresistance. Results: miRNA microarray analysis identified four upregulated miRNAs and 20 downregulated miRNAs in chemoresistant patients compared to chemosensitive patients. Twelve markedly dysregulated miRNAs were selected for further investigation, of which six (miR-100, miR-92a, miR-16, miR-30e, miR-144-5p, and let-7i) were verified to be significantly and consistently dysregulated (>1.5-fold, P < 0.05). The combination of the six miRNAs had the highest AUC (0.825, 95% CI, 0.753-0.897). The expression level of these 6 miRNAs was not correlated with tumor location, stage, or chemotherapy program. Only miR-100 was significantly upregulated in low histological grade. GO analysis and KEGG pathway analysis showed that miRNAs were related to RNA polymerase II transcription and enriched in the PI3K-AKT signaling pathway, AMPK signaling pathway, and FoxO signaling pathway. Conclusions: We identified a panel of plasma exosomal miRNAs, containing miR-100, miR-92a, miR-16, miR-30e, miR-144-5p, and let-7i, that could significantly distinguish chemoresistant patients from chemosensitive patients. The detection of circulating exosomal miRNAs may serve as an effective way to monitor CRC patient responses to chemotherapy. Targeting these miRNAs may also be a promising strategy for CRC treatment.

Project description:BackgroundCopper (Cu) and zinc (Zn) are essential nutrients and cofactors of enzymatic reactions with their binding partner. Metallothionein (MT) plays an important role in protecting against heavy metals and oxidative injury, however it may also portend drug resistance and a worse prognosis for hepatocellular carcinoma (HCC) patients. The aim of this study was to determine the amount of Cu, Zn, Cu/Zn and MT in evaluating a group of patients with HCC, including those treated with lenvatinib.MethodsWe enrolled 175 patients with HCC (139 men, 36 women; mean age 71.1 years; hepatitis C virus n = 85, hepatitis B virus n = 19, hepatitis C virus and hepatitis B virus n = 2, non-alcoholic steatohepatitis n = 39, alcohol n = 25, others n = 5; Child-Pugh A n = 141, Child-Pugh B n = 30, Child-Pugh C n = 4; Barcelona clinic liver cancer (BCLC) stage 0 n = 38, stage A n = 56, stage B n = 39, stage C n = 38, stage D n = 4). We evaluated the associations between Cu, Zn and MT. The study outcome was liver cancer-specific survival. Moreover, we treated 12 HCC patients with lenvatinib and investigated the changes in MT during lenvatinib therapy.ResultsThe serum level of Cu was positively correlated with alanine aminotransferase and the BCLC stage. The serum level of Zn decreased concordant with liver disease progression. Patients with a Cu/Zn ratio≥0.999 had significantly improved rates of survival when compared to patients with a Cu/Zn ratio<0.999 (45.3 vs. 30.1 months, p<0.001). MT was significantly correlated with the Cu/Zn ratio and increased after the administration of lenvatinib. Using multivariate Cox regression analyses, it was determined that the Cu/Zn ratio (hazard ratio [HR]: 1.442, p = 0.008), alpha-fetoprotein (HR: 1.000, p<0.001) and BCLC stage (HR: 2.087, p<0.001) were independent predictors of survival.ConclusionsThe Cu/Zn ratio could serve as a useful predictive marker for survival in cases of HCC. MT levels increased in HCC patients receiving lenvatinib therapy, and maybe a predictor of reduced survival.

Dataset Information

Circulating plasma exosomal miRNA profiles serve as potential metastasis-related biomarkers for hepatocellular carcinoma.

Publications

Circulating plasma exosomal miRNA profiles serve as potential metastasis-related biomarkers for hepatocellular carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets