Up-Regulation of hsa-miR-210 Promotes Venous Metastasis and Predicts Poor Prognosis in Hepatocellular Carcinoma

Objective: To investigate the potential biomarkers for venous metastasis of hepatocellular carcinoma (HCC), and briefly discuss their target genes and the signaling pathways they are involved in.Materials and Method: The dataset GSE6857 was downloaded from GEO. Significantly differentially expressed...

Full description

Bibliographic Details
Main Authors: Jia Ji, Yuan Rong, Chang-Liang Luo, Shuo Li, Xiang Jiang, Hong Weng, Hao Chen, Wu-Wen Zhang, Wen Xie, Fu-Bing Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-12-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2018.00569/full
_version_ 1818152299967545344
author Jia Ji
Jia Ji
Yuan Rong
Chang-Liang Luo
Shuo Li
Xiang Jiang
Hong Weng
Hao Chen
Wu-Wen Zhang
Wen Xie
Fu-Bing Wang
author_facet Jia Ji
Jia Ji
Yuan Rong
Chang-Liang Luo
Shuo Li
Xiang Jiang
Hong Weng
Hao Chen
Wu-Wen Zhang
Wen Xie
Fu-Bing Wang
author_sort Jia Ji
collection DOAJ
description Objective: To investigate the potential biomarkers for venous metastasis of hepatocellular carcinoma (HCC), and briefly discuss their target genes and the signaling pathways they are involved in.Materials and Method: The dataset GSE6857 was downloaded from GEO. Significantly differentially expressed miRNAs were identified using the R package “limma,” After that, the survival analysis was conducted to discover the significance of these up-regulated miRNAs for the prognosis of HCC patients. Additionally, miRNAs which were up-regulated in venous metastasis positive HCC tissues and were significant for the prognosis of HCC patients were further verified in clinical samples using RT-qPCR. The miRNAs were then analyzed for their correlations with clinical characteristics including survival time, AFP level, pathological grade, TNM stage, tumor stage, lymph-node metastasis, distant metastasis, child-pugh score, vascular invasion, liver fibrosis and race using 375 HCC samples downloaded from the TCGA database. The target genes of these miRNAs were obtained using a miRNA target gene prediction database, and their functions were analyzed using the online tool DAVID.Results: 15 miRNAs were differentially expressed in samples with venous metastasis, among which 7 were up-regulated in venous metastasis positive HCC samples. As one of the up-regulated miRNAs, hsa-miR-210 was identified as an independent prognostic factor for HCC. Using RT-qPCR, it was evident that hsa-miR-210 expression was significantly higher in venous metastasis positive HCC samples (p = 0.0036). Further analysis indicated that hsa-miR-210 was positively associated with AFP level, pathological grade, TNM stage, tumor stage and vascular invasion. A total of 168 hsa-miR-210 target genes, which are mainly related to tumor metastasis and tumor signaling pathways, were also predicted in this study.Conclusion: hsa-miR-210 might promote vascular invasion of HCC cells and could be used as a prognostic biomarker.
first_indexed 2024-12-11T13:52:31Z
format Article
id doaj.art-660457fbfbe64111b2eee44b632ca3ba
institution Directory Open Access Journal
issn 2234-943X
language English
last_indexed 2024-12-11T13:52:31Z
publishDate 2018-12-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj.art-660457fbfbe64111b2eee44b632ca3ba2022-12-22T01:04:13ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2018-12-01810.3389/fonc.2018.00569414225Up-Regulation of hsa-miR-210 Promotes Venous Metastasis and Predicts Poor Prognosis in Hepatocellular CarcinomaJia Ji0Jia Ji1Yuan Rong2Chang-Liang Luo3Shuo Li4Xiang Jiang5Hong Weng6Hao Chen7Wu-Wen Zhang8Wen Xie9Fu-Bing Wang10Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Laboratory Medicine, Wuhan Children's Hospital, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaCenter for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaObjective: To investigate the potential biomarkers for venous metastasis of hepatocellular carcinoma (HCC), and briefly discuss their target genes and the signaling pathways they are involved in.Materials and Method: The dataset GSE6857 was downloaded from GEO. Significantly differentially expressed miRNAs were identified using the R package “limma,” After that, the survival analysis was conducted to discover the significance of these up-regulated miRNAs for the prognosis of HCC patients. Additionally, miRNAs which were up-regulated in venous metastasis positive HCC tissues and were significant for the prognosis of HCC patients were further verified in clinical samples using RT-qPCR. The miRNAs were then analyzed for their correlations with clinical characteristics including survival time, AFP level, pathological grade, TNM stage, tumor stage, lymph-node metastasis, distant metastasis, child-pugh score, vascular invasion, liver fibrosis and race using 375 HCC samples downloaded from the TCGA database. The target genes of these miRNAs were obtained using a miRNA target gene prediction database, and their functions were analyzed using the online tool DAVID.Results: 15 miRNAs were differentially expressed in samples with venous metastasis, among which 7 were up-regulated in venous metastasis positive HCC samples. As one of the up-regulated miRNAs, hsa-miR-210 was identified as an independent prognostic factor for HCC. Using RT-qPCR, it was evident that hsa-miR-210 expression was significantly higher in venous metastasis positive HCC samples (p = 0.0036). Further analysis indicated that hsa-miR-210 was positively associated with AFP level, pathological grade, TNM stage, tumor stage and vascular invasion. A total of 168 hsa-miR-210 target genes, which are mainly related to tumor metastasis and tumor signaling pathways, were also predicted in this study.Conclusion: hsa-miR-210 might promote vascular invasion of HCC cells and could be used as a prognostic biomarker.https://www.frontiersin.org/article/10.3389/fonc.2018.00569/fullhsa-miR-210venous metastasisprognosishepatocellular carcinomabioinformatics analysisRT-qPCR
spellingShingle Jia Ji
Jia Ji
Yuan Rong
Chang-Liang Luo
Shuo Li
Xiang Jiang
Hong Weng
Hao Chen
Wu-Wen Zhang
Wen Xie
Fu-Bing Wang
Up-Regulation of hsa-miR-210 Promotes Venous Metastasis and Predicts Poor Prognosis in Hepatocellular Carcinoma
Frontiers in Oncology
hsa-miR-210
venous metastasis
prognosis
hepatocellular carcinoma
bioinformatics analysis
RT-qPCR
title Up-Regulation of hsa-miR-210 Promotes Venous Metastasis and Predicts Poor Prognosis in Hepatocellular Carcinoma
title_full Up-Regulation of hsa-miR-210 Promotes Venous Metastasis and Predicts Poor Prognosis in Hepatocellular Carcinoma
title_fullStr Up-Regulation of hsa-miR-210 Promotes Venous Metastasis and Predicts Poor Prognosis in Hepatocellular Carcinoma
title_full_unstemmed Up-Regulation of hsa-miR-210 Promotes Venous Metastasis and Predicts Poor Prognosis in Hepatocellular Carcinoma
title_short Up-Regulation of hsa-miR-210 Promotes Venous Metastasis and Predicts Poor Prognosis in Hepatocellular Carcinoma
title_sort up regulation of hsa mir 210 promotes venous metastasis and predicts poor prognosis in hepatocellular carcinoma
topic hsa-miR-210
venous metastasis
prognosis
hepatocellular carcinoma
bioinformatics analysis
RT-qPCR
url https://www.frontiersin.org/article/10.3389/fonc.2018.00569/full
work_keys_str_mv AT jiaji upregulationofhsamir210promotesvenousmetastasisandpredictspoorprognosisinhepatocellularcarcinoma
AT jiaji upregulationofhsamir210promotesvenousmetastasisandpredictspoorprognosisinhepatocellularcarcinoma
AT yuanrong upregulationofhsamir210promotesvenousmetastasisandpredictspoorprognosisinhepatocellularcarcinoma
AT changliangluo upregulationofhsamir210promotesvenousmetastasisandpredictspoorprognosisinhepatocellularcarcinoma
AT shuoli upregulationofhsamir210promotesvenousmetastasisandpredictspoorprognosisinhepatocellularcarcinoma
AT xiangjiang upregulationofhsamir210promotesvenousmetastasisandpredictspoorprognosisinhepatocellularcarcinoma
AT hongweng upregulationofhsamir210promotesvenousmetastasisandpredictspoorprognosisinhepatocellularcarcinoma
AT haochen upregulationofhsamir210promotesvenousmetastasisandpredictspoorprognosisinhepatocellularcarcinoma
AT wuwenzhang upregulationofhsamir210promotesvenousmetastasisandpredictspoorprognosisinhepatocellularcarcinoma
AT wenxie upregulationofhsamir210promotesvenousmetastasisandpredictspoorprognosisinhepatocellularcarcinoma
AT fubingwang upregulationofhsamir210promotesvenousmetastasisandpredictspoorprognosisinhepatocellularcarcinoma