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Identification of recurrence-related serum microRNAs in hepatocellular carcinoma following hepatectomy.

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most deadly tumors. Prognosis of patients with HCC is generally poor due to the high recurrence rate. In the present study, TaqMan Real-time PCR microRNA Array was used to identify differentially expressed miRNAs from 10 tumor tissue samples (5 from recurrence group vs. 5 from non-recurrence group) and the matched serum samples. Four differentially expressed miRNAs (miR-486-5p, miR-422a, miR-125b and miR-139-5p) were further quantified in 20 tumor tissues and 116 HCC patients' serum before they received hepatectomy. Univariate analysis revealed that miR-486-5p, miR-422a and miR-125b were significantly associated with patients' relapse free survival (RFS). Multivariate analysis demonstrated that miR-486-5p, AFP and microvascular invasion (MVI) were the independent prognostic factors associated with RFS in this cohort (p = 0.000, 0.043, 0.000, respectively). Besides, the expression levels of miR-486-5p were positively correlated in tumor tissues and the paired serum samples, so was miR-422a. The probability of the prognostic accuracy of miR-486-5p in predicting postoperative recurrence of HCC within the first year was 76.79% (65.38% specificity and 81.58% sensitivity), which was almost equal to the classifier established by combination of AFP and MVI (75.98% probability, 63.13% specificity and 85.90% sensitivity). Furthermore, the combination of AFP, MVI and miR-486-5p yielded a ROC curve area of 88.02% (69.20% specificity and 92.10% sensitivity). Our study was the first to identify that serum miR-486-5p could be used to stratify the patients with higher recurrence risk before hepatic resection and potentially guide more effective surveillance strategies for them.

SUBMITTER: Wang L

PROVIDER: S-EPMC4846138 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Identification of recurrence-related serum microRNAs in hepatocellular carcinoma following hepatectomy.

Wang Liming L Liu Mei M Zhu Hongxia H Rong Weiqi W Wu Fan F An Songlin S Liu Faqiang F Feng Li L Wu Jianxiong J Xu Ningzhi N

Cancer biology & therapy 20150715 10

Hepatocellular carcinoma (HCC) is one of the most deadly tumors. Prognosis of patients with HCC is generally poor due to the high recurrence rate. In the present study, TaqMan Real-time PCR microRNA Array was used to identify differentially expressed miRNAs from 10 tumor tissue samples (5 from recurrence group vs. 5 from non-recurrence group) and the matched serum samples. Four differentially expressed miRNAs (miR-486-5p, miR-422a, miR-125b and miR-139-5p) were further quantified in 20 tumor tis ...[more]

PMID: 26176380

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Project description:Background and aimsPrimary hepatocellular carcinoma (HCC) is usually presented in inflamed fibrotic/cirrhotic liver with extensive lymphocyte infiltration. We examined the associations between the HCC early recurrence and alterations in serum levels of inflammatory cytokines.MethodsA cohort of 105 HCC patients with chronic hepatitis B virus infection were included. Pre-therapy, we quantified their serum concentrations of Th1-, Th2-, Th17-, Treg-related, and other cytokines that have been reported to be associated with poor prognosis in human cancers. IL17-producing T-cells were generated in vitro from HCC patients and co-cultured with HCC cell lines separated by a 0.4 µM transwell.ResultsAll the 105 cases of HCC patients had liver cirrhosis. The patients who suffered from HCC early recurrence had higher pre-therapy serum levels of IL17 and lower levels of IL10 than those who did not suffer from recurrence after curative hepatectomy. After adjustment for general tumor clinicopathological factors, elevated serum levels of IL17 (? 0.9 pg/ml) was found to be an independent risk factor for HCC early recurrence with a hazard ratio of 2.46 (95%CI 1.34-4.51). Patients with bigger tumors (>5 cm in diameter) and elevated serum levels of IL17 had the highest risk of early recurrence as compared to those with only one of these factors (P = 0.009) or without any (P<0.001). These factors showed similar effects on the HCC patient overall survival. Intrahepatic infiltrated T-cells in HCC patients were identified as the major IL17-producing cells. Proliferation of HCC cells, QGY-7703, was augmented QGY-7703, was augmented in the presence of IL17-producing T-cells. This effect diminished after neutralizing antibody against human IL17A or TNF? was included.ConclusionBoth tumors and IL17 from liver infiltrated T-cells contributed to HCC early recurrence and progression after curative resection. Pre-therapy serum IL17 levels may serve as an additional indicator for predicting high-risk patients.

Dataset Information

Identification of recurrence-related serum microRNAs in hepatocellular carcinoma following hepatectomy.

Publications

Identification of recurrence-related serum microRNAs in hepatocellular carcinoma following hepatectomy.

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