A glycolysis-related gene pairs signature predicts prognosis in patients with hepatocellular carcinoma

PeerJ. 2020 Sep 29:8:e9944. doi: 10.7717/peerj.9944. eCollection 2020.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most universal malignant liver tumors worldwide. However, there were no systematic studies to establish glycolysis‑related gene pairs (GRGPs) signatures for the patients with HCC. Therefore, the study aimed to establish novel GRGPs signatures to better predict the prognosis of HCC.

Methods: Based on the data from Gene Expression Omnibus, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium databases, glycolysis-related mRNAs were used to construct GRGPs. Cox regression was applied to establish a seventeen GRGPs signature in TCGA dataset, which was verified in two validation (European and American, and Asian) datasets.

Results: Seventeen prognostic GRGPs (HMMR_PFKFB1, CHST1_GYS2, MERTK_GYS2, GPC1_GYS2, LDHA_GOT2, IDUA_GNPDA1, IDUA_ME2, IDUA_G6PD, IDUA_GPC1, MPI_GPC1, SDC2_LDHA, PRPS1_PLOD2, GALK1_IER3, MET_PLOD2, GUSB_IGFBP3, IL13RA1_IGFBP3 and CYB5A_IGFBP3) were identified to be significantly progressive factors for the patients with HCC in the TCGA dataset, which constituted a GRGPs signature. The patients with HCC were classified into low-risk group and high-risk group based on the GRGPs signature. The GRGPs signature was a significantly independent prognostic indicator for the patients with HCC in TCGA (log-rank P = 2.898e-14). Consistent with the TCGA dataset, the patients in low-risk group had a longer OS in two validation datasets (European and American: P = 1.143e-02, and Asian: P = 6.342e-08). Additionally, the GRGPs signature was also validated as a significantly independent prognostic indicator in two validation datasets.

Conclusion: The seventeen GRGPs and their signature might be molecular biomarkers and therapeutic targets for the patients with HCC.

Keywords: GRGPs signature; Glycolysis; Hepatocellular carcinoma; Prognosis; mRNAs.

Grants and funding

This study was funded by the National Natural Science Foundation of China (81774451), the Natural Science Foundation of Guangdong Province (2017A030313827), and the Science Program for Overseas Scholar (Xinhuo plan) of Guangzhou University of Chinese Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.