A glycolysis-based three-gene signature predicts survival in patients with lung squamous cell carcinoma

Guichuan Huang,Yi Huang,Ling Gong,Daishun Liu,Jing Zhang

doi:10.1186/s12885-021-08360-z

Guichuan Huang, Yi Huang + Show 3 more

Open Access

https://doi.org/10.1186/s12885-021-08360-z

Copy DOI

Abstract

BackgroundLung cancer is one of the most lethal and most prevalent malignant tumors worldwide, and lung squamous cell carcinoma (LUSC) is one of the major histological subtypes. Although numerous biomarkers have been found to be associated with prognosis in LUSC, the prediction effect of a single gene biomarker is insufficient, especially for glycolysis-related genes. Therefore, we aimed to develop a novel glycolysis-related gene signature to predict survival in patients with LUSC.MethodsThe mRNA expression files and LUSC clinical information were obtained from The Cancer Genome Atlas (TCGA) dataset.ResultsBased on Gene Set Enrichment Analysis (GSEA), we found 5 glycolysis-related gene sets that were significantly enriched in LUSC tissues. Univariate and multivariate Cox proportional regression models were performed to choose prognostic-related gene signatures. Based on a Cox proportional regression model, a risk score for a three-gene signature (HKDC1, ALDH7A1, and MDH1) was established to divide patients into high-risk and low-risk subgroups. Multivariate Cox regression analysis indicated that the risk score for this three-gene signature can be used as an independent prognostic indicator in LUSC. Additionally, based on the cBioPortal database, the rate of genomic alterations in the HKDC1, ALDH7A1, and MDH1 genes were 1.9, 1.1, and 5% in LUSC patients, respectively.ConclusionA glycolysis-based three-gene signature could serve as a novel biomarker in predicting the prognosis of patients with LUSC and it also provides additional gene targets that can be used to cure LUSC patients.

Highlights

Lung cancer is one of the most lethal and most prevalent malignant tumors worldwide, and lung squamous cell carcinoma (LUSC) is one of the major histological subtypes
Initial screening of genes by Gene Set Enrichment Analysis (GSEA) The mRNA expression data set and clinical information for 501 patients with LUSC were obtained from the The Cancer Genome Atlas (TCGA) database (Fig. 1)
Identification of glycolysis-related genes associated with patient survival First, univariate Cox proportional hazard regression analysis was conducted for 443 genes that were significantly enriched in LUSC samples from the GSEA

Summary

Introduction

Lung cancer is one of the most lethal and most prevalent malignant tumors worldwide, and lung squamous cell carcinoma (LUSC) is one of the major histological subtypes. Numerous biomarkers have been found to be associated with prognosis in LUSC, the prediction effect of a single gene biomarker is insufficient, especially for glycolysis-related genes. The cells obtain energy via glycolysis instead of oxygen-consuming mitochondrial metabolism [6]. Glycolysis, known as the Warburg effect, is often observed in human cancer cells, in which the cancer cells favor glucose metabolism via glycolysis even in the presence of oxygen [7]. This phenomenon is a unique energy metabolism that exists in cancer cells. Many biomarkers for LUSC have been discovered, including glycolysis-associated genes such as kininogen 1 (KNG1) [8] and tripartite motif-containing protein 59 (TRIM59) [9]

Objectives

Methods

Results

Conclusion