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Cellular Oncology
Published in: Cellular Oncology 2/2020

Open Access 01-04-2020 | Hepatocellular Carcinoma | Original paper

Multiple novel hepatocellular carcinoma signature genes are commonly controlled by the master pluripotency factor OCT4

Authors: Chao Ye, Xiaoqian Zhang, Xinyu Chen, Qingyi Cao, Xiaobing Zhang, Yanwen Zhou, Wenxin Li, Liangjie Hong, Haiyang Xie, Xiaoli Liu, Hongcui Cao, Ying-Jie Wang, Bo Kang

Published in: Cellular Oncology | Issue 2/2020

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Abstract

Background

Worldwide, hepatocellular carcinoma (HCC) is a common solid tumor with a poor prognosis. HCC is often due to hepatitis B virus (HBV) infection. As yet, efficacious HCC treatment regimens for late-stage HCC patients are lacking. Therefore, the identification of more specific and sensitive biomarkers for its early diagnosis and treatment remains an urgent need.

Methods

Total RNAs from paired HBV-derived HCC tumors and adjacent peritumor tissues (APTs) were subjected to RNA sequencing (RNA-seq), and differentially expressed genes (DEGs) between HCC tumors and APTs were selected and verified.

Results

We identified 166 DEGs and found that eight top-ranked and verified DEGs (TK1, CTTN, CEP72, TRIP13, FTH1, FLAD1, CHRM2, AMBP) all contained putative OCT4 binding motifs in their promoter regions. TK1, TRIP13 and OCT4 were found to exhibit concurrent higher expression levels in HCC tumors than in APTs. The mRNA levels of TK1, TRIP13 and OCT4 in a cohort of 384 HCC samples from the TCGA database were all found to be negatively correlated with patient overall survival, relapse-free survival and progression-free survival, underscoring the HCC biomarker status of TK1 and TRIP13 on one hand, and implicating their association with OCT4 on the other hand. Furthermore, OCT4 proteins were found to bind to the promoters of both genes in vitro and in vivo. Knocking out OCT4 in HCC-derived cell lines reduced the expression of TK1 and TRIP13 and significantly decreased their tumorigenicity.

Conclusions

Using RNA-seq, we identified several novel HCC signature genes that may serve as biomarkers for its diagnosis and prognosis. Their common transcriptional regulation by OCT4 suggests key roles in the development of HCC, and indicates that OCT4 may serve as a potential therapeutic target.
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Metadata
Title
Multiple novel hepatocellular carcinoma signature genes are commonly controlled by the master pluripotency factor OCT4
Authors
Chao Ye
Xiaoqian Zhang
Xinyu Chen
Qingyi Cao
Xiaobing Zhang
Yanwen Zhou
Wenxin Li
Liangjie Hong
Haiyang Xie
Xiaoli Liu
Hongcui Cao
Ying-Jie Wang
Bo Kang
Publication date
01-04-2020
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 2/2020
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-019-00487-3

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