Dataset Information

Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma.

ABSTRACT: The long-term survival rate of hepatocellular carcinoma (HCC) is poor. One of the reasons for the poor rate of survival is the high rate of recurrence caused by intrahepatic metastas is that adversely affects long-term outcome. Many studies have indicated that microRNAs play an important role in HCC, but there has been no research of clonal origins on recurrent HCC (RHCC) by analzing microRNAs. In the present study, we found that miR-483-5p was significantly upregulated in RHCC tissues of short-term recurrence (? 2 years) by miRNA microarray screening, and can significantly promote migration and invasion of HCC cells in vitro and increase intrahepatic metastasis in nude mice in vivo. Furthermore, we demonstrated that activated leukocyte cell adhesion molecule (ALCAM), which significantly suppressed migration and invasion of HCC cells, was a direct target of miR-483-5p, and the re-introduction of ALCAM expression could antagonize the promoting effects of miR-483-5p on the capacity of HCC cells for migration and invasion. In addition, expression level of ALCAM was negatively correlated with microvascular invasion and tumor size recognized as prognostic factors. The cases which were negative for ALCAM expression had shorter time to recurrence than positive cases, and univariate and multivariate survival analyses showed that ALCAM was an independent risk factor of HCC recurrence. qRT-PCR and Western blotting showed that the expression of EMT related genes (MMP-2, MMP-9, E-caherin and vimentin) significantly changed as a result of interfering or overexpression of ALCAM, and ALCAM was significantly associated with EMT in HCC. These results suggest that the miR-483-5p/ALCAM axis is an important regulator in invasion and metastasis and biomarker for recurrence risk assessment of HCC.

SUBMITTER: Lu XY

PROVIDER: S-EPMC5770356 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma.

Lu Xin-Yuan XY Chen Di D Gu Xiao-Yuan XY Ding Jie J Zhao Ying-Jun YJ Zhao Qian Q Yao Ming M Chen Zhiao Z He Xiang-Huo XH Cong Wen-Ming WM

Frontiers in pharmacology 20180112

The long-term survival rate of hepatocellular carcinoma (HCC) is poor. One of the reasons for the poor rate of survival is the high rate of recurrence caused by intrahepatic metastas is that adversely affects long-term outcome. Many studies have indicated that microRNAs play an important role in HCC, but there has been no research of clonal origins on recurrent HCC (RHCC) by analzing microRNAs. In the present study, we found that miR-483-5p was significantly upregulated in RHCC tissues of short- ...[more]

PMID: 29375378

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Project description: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.

Project description:BackgroundFew studies have focused on the prognosis of patients with hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage 0‒C in terms of early recurrence and 5-years overall survival (OS). We sought to develop nomograms for predicting 5-year OS and early recurrence after curative resection of HCC, based on a clinicopathological‒radiological model. We also investigated whether different treatment methods influenced the OS of patients with early recurrence.MethodsRetrospective data, including clinical pathology, radiology, and follow-up data, were collected for 494 patients with HCC who underwent hepatectomy. Nomograms estimating OS and early recurrence were constructed using multivariate Cox regression analysis, based on the random survival forest (RSF) model. We evaluated the discrimination and calibration abilities of the nomograms using concordance indices (C-index), calibration curves, and Kaplan‒Meier curves. OS curves of different treatments for patients who had recurrence within 2 years after curative surgery were depicted and compared using the Kaplan-Meier method and the log-rank test.ResultsMultivariate Cox regression revealed that BCLC stage, non-smooth margin, maximum tumor diameter, age, aspartate aminotransferase levels, microvascular invasion, and differentiation were prognostic factors for OS and were incorporated into the nomogram with good predictive performance in the training (C-index: 0.787) and testing cohorts (C-index: 0.711). A nomogram for recurrence-free survival was also developed based on four prognostic factors (BCLC stage, non-smooth margin, maximum tumor diameter, and microvascular invasion) with good predictive performance in the training (C-index: 0.717) and testing cohorts (C-index: 0.701). In comparison to the BCLC staging system, the C-index (training cohort: 0.787 vs. 0.678, 0.717 vs. 0.675; external cohort 2: 0.748 vs. 0.624, 0.729 vs. 0.587 respectively, for OS and RFS; external cohort1:0.716 vs. 0.627 for RFS, all p value<0.05), and model calibration curves all showed improved performance. Patients who underwent surgery after tumor recurrence had a higher reOS than those who underwent comprehensive treatments and supportive care.ConclusionsThe nomogram, based on clinical, pathological, and radiological factors, demonstrated good accuracy in estimating OS and recurrence, which can guide follow-up and treatment of individual patients. Reoperation may be the best option for patients with recurrence in good condition.

Dataset Information

Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma.

Publications

Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma.

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