AUTHOR=Li Jian-Hua , Tao Yi-Feng , Shen Cong-Huan , Li Rui-Dong , Wang Zheng , Xing Hao , Ma En-Si , Xue Hong-Yuan , Zhang Quan-Bao , Ma Zhen-Yu , Wang Zheng-Xin 

TITLE=Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.939948

DOI=10.3389/fonc.2022.939948

ISSN=2234-943X

ABSTRACT=<p>Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a high recurrence rate. Accurate prediction of recurrence risk is urgently required for tailoring personalized treatment programs for individual HCC patients in advance. In this study, we analyzed a gene expression dataset from an HCC cohort with 247 samples and identified five genes including <italic>ENY2</italic>, <italic>GPAA1</italic>, <italic>NDUFA4L2</italic>, <italic>NEDD9</italic>, and <italic>NRP1</italic> as the variables for the prediction of HCC recurrence, especially the early recurrence. The Cox model and risks score were validated in two public HCC cohorts (GSE76427 and The Cancer Genome Atlas (TCGA)) and one cohort from Huashan Hospital, which included a total of 641 samples. Moreover, the multivariate Cox regression analysis revealed that the risk score could serve as an independent prognostic factor in the prediction of HCC recurrence. In addition, we found that <italic>ENY2</italic>, <italic>GPAA1</italic>, and <italic>NDUFA4L2</italic> were significantly upregulated in HCC of the two validation cohorts, and <italic>ENY2</italic> had significantly higher expression levels than another four genes in malignant cells, suggesting that <italic>ENY2</italic> might play key roles in malignant cells. The cell line analysis revealed that ENY2 could promote cell cycle progression, cell proliferation, migration, and invasion. The functional analysis of the genes correlated with <italic>ENY2</italic> revealed that ENY2 might be involved in telomere maintenance, one of the fundamental hallmarks of cancer. In conclusion, our data indicate that ENY2 may regulate the malignant phenotypes of HCC <italic>via</italic> activating telomere maintenance.</p>