J Cancer 2020; 11(14):4145-4156. doi:10.7150/jca.41983

Research Paper

Predictive value of hypoxia, metabolism and immune factors for prognosis in hepatocellular carcinoma: a retrospective analysis and multicenter validation study

Peng Lin1, Dong-yue wen1, Gang Chen2, Yi-wu Dang2, Yun He1, Hong Yang1✉

1. Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
2. Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.

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Citation:
Lin P, wen Dy, Chen G, Dang Yw, He Y, Yang H. Predictive value of hypoxia, metabolism and immune factors for prognosis in hepatocellular carcinoma: a retrospective analysis and multicenter validation study. J Cancer 2020; 11(14):4145-4156. doi:10.7150/jca.41983. Available from http://www.jcancer.org/v11p4145.htm

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Abstract

The tumor microenvironment (TME), as a potent and pervasive factor of tumorigenesis and tumor progression, has a profound impact on the clinical outcomes of hepatocellular carcinoma (HCC). A systematic analysis of TME factors in HCC is still lacking and urgently needed. In this retrospective analysis and multicenter validation study, a total of 987 HCC patients with RNA-seq or microarray data and the corresponding clinical information from five cohorts were included. A TME risk score was developed based on five factors (hypoxia, nucleotide, TCA cycle, T helper cells and activated CD8 T cells). We also identified various types of clinical parameters and molecular features associated with the TME risk score. The TME risk factor network depicts close associations among the factors. Our TME risk score could be a practical and reliable predictor that can stratify patients according to distinct clinical outcomes and was validated by integrating five HCC patient cohorts (HR= 2.27, 95% CI: 1.79-2.86, P<0.001). Pan-cancer analysis also suggested that the prognostic signature was an effective prognostic indicator in 9,122 patients across 30 types of cancer. Correlation analysis revealed that the TME risk score was significantly associated with tumor progression-related clinical factors and molecular factors. TME factors are perturbations in HCC patients, and these alterations are vital determinants of both clinical outcomes and biological characteristics. The TME risk score we proposed is valuable for deciphering the molecular characteristics of the TME in HCC and is an effective prognostic predictor for HCC prognosis evaluation.

Keywords: hepatocellular carcinoma, tumor microenvironment, prognosis, multi-omics data.