A robust nine-gene prognostic signature associated with tumour doubling time for hepatocellular carcinoma

Tumour doubling time (TDT) is an indicator reflecting tumour growth rate, however, the prognostic genes associated with the TDT in hepatocellular carcinoma (HCC) have not been fully identified.

We obtained mRNA expression profiles and tumour doubling time from GSE54236 and used the Pearson correlation test to identify tumour doubling time-related genes (TDTRGs). We extracted TDTRGs from The Cancer Genome Atlas (TCGA) and identified prognostic genes using univariate Cox regression analysis and Kaplan-Meier survival analysis. Lasso and multivariate Cox regression analysis assisted in constructing the signature and International Cancer Genome Consortium (ICGC) served as an external validation.

We identified a total of 296 genes associated with tumour doubling time and developed a prognostic signature consisting of 9 genes. Patients were divided into high- and low-risk groups according to the uniform cutoff (0.85). Regardless of the clinical characteristics of the patients, the group at high risk exhibited obviously lower overall survival (OS) than did the group with low risk in both TCGA and ICGC cohorts. The prognostic model showed superior accuracy in both TCGA and ICGC cohorts, as confirmed by receiver operating characteristic (ROC) curve analysis. The univariate together with multivariate Cox regression analysis further suggested the ability of the signature to predict prognosis independently.

A novel prognostic signature for HCC was developed and validated in the study, which may be beneficial to improve the treatment strategy of HCC.