Transcriptomic profiling of peroxisome-related genes reveals a novel prognostic signature in hepatocellular carcinoma

Abstract

Emerging evidence suggests that peroxisomes play a role in the regulation of tumorigenesis and cancer progression. However, the prognostic value of peroxisome-related genes has been rarely investigated. This study aimed to establish a peroxisome-related gene signature for overall survival (OS) prediction in patients with hepatocellular carcinoma (HCC). First, univariate Cox regression analysis was employed to identify prognostic peroxisome-related genes in The Cancer Genome Atlas liver cancer cohort, and least absolute shrinkage and selection operator Cox regression analysis was used to construct a 10-gene signature. The risk score based on the signature was positively correlated with poor prognosis (HR = 4.501, 95% CI = 3.021–6.705, P = 1.39e−13). Second, multivariate Cox regression incorporating additional characteristics revealed that the signature was an independent predictor. Time-dependent ROC curves demonstrated good performance of the signature in predicting the OS of HCC patients. The prognostic performance was validated using International Cancer Genome Consortium HCC cohort data. Gene set enrichment analysis revealed that the signature-related alterations in biological processes mainly involved peroxisomal functions. Finally, we developed a nomogram model based on the gene signature and TNM stage, which showed a superior prognostic power (C-index = 0.702). Thus, our study revealed a novel peroxisome-related gene signature that may help improve personalized OS prediction in HCC patients.

Keywords

• Gene signature
• Hepatocellular carcinoma
• Nomogram
• Peroxisome
• Prognosis