Construction and validation of a prognostic signature using CNV-driven genes for hepatocellular carcinoma

Jin Bian; Junyu Long; Xu Yang; Xiaobo Yang; Yiyao Xu; Xin Lu; Mei Guan; Xinting Sang; Haitao Zhao

doi:10.21037/atm-20-7101

Construction and validation of a prognostic signature using CNV-driven genes for hepatocellular carcinoma

Ann Transl Med. 2021 May;9(9):765. doi: 10.21037/atm-20-7101.

Authors

Jin Bian¹, Junyu Long¹, Xu Yang¹, Xiaobo Yang¹, Yiyao Xu¹, Xin Lu¹, Mei Guan², Xinting Sang¹, Haitao Zhao¹

Affiliations

¹ Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.
² Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related deaths worldwide. Copy number variations (CNVs) affect the expression of genes and play critical roles in carcinogenesis. We aimed to identify specific CNV-driven genes and establish a prognostic model for HCC.

Methods: Integrative analysis of CNVs difference data and differentially expressed genes (DEGs) data from The Cancer Genome Atlas (TCGA) were conducted to identify critical CNV-driven genes for HCC. A risk model was constructed based on univariate Cox regression analysis, Least Absolute Shrinkage and Selection Operator (LASSO), and multivariate Cox regression analyses. The associations between CNV-driven genes signature and infiltrating immune cells were explored. The International Cancer Genome Consortium (ICGC) dataset was utilized to validate this model.

Results: After integrative analysis of CNVs and corresponding mRNA expression profiles, 568 CNV-driven genes were identified. Sixty-three CNV-driven genes were found to be markedly associated with overall survival (OS) after univariate Cox regression analysis. Finally, eight CNV-driven genes were screened to generate a prognostic risk model. Compared with low-risk group, the OS of patients in the high-risk group was significantly shorter in both the TCGA [hazard ratio (HR) =6.14, 95% confidence interval (CI): 2.72-13.86, P<0.001] and ICGC (HR =3.23, 95% CI: 1.17-8.92, P<0.001) datasets. Further analysis revealed the infiltrating neutrophils were positively correlated with risk score. Meanwhile, the high-risk group was associated with higher expression of immune checkpoint genes.

Conclusions: A novel signature based on CNV-driven genes was built to predict the survival of HCC patients and showed good performance. The results of our study may improve understanding of the mechanism that drives HCC, and provide an immunological perspective for individualized therapies.

Keywords: Copy number variation-driven genes (CNV-driven genes); hepatocellular carcinoma (HCC); immune microenvironment; prognosis.