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

Abstract

Background 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. 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. Methods The mRNA expression files and LUSC clinical information were obtained from The Cancer Genome Atlas (TCGA) dataset. Results Based 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. Conclusion A 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.

Determination of a prediction model for therapeutic response and prognosis based on chemokine signaling-related genes in stage I–III lung squamous cell carcinoma

“…Furthermore, we compared the performance of the present signature with those of the other previously reported gene signatures in LUSC. The RMS curve showed that the performance of the present signature was similar to that of the other four signatures ( Supplementary Figure S3C ) ( Huang et al, 2021 ; Li et al, 2021 ; Li et al, 2022 ; Zhai et al, 2022 ). These results suggest that the CSRG signature can serve as a candidate prognostic biomarker for survival in patients with stage I–III LUSC.…”

A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs

“…Human malignancies, including LUSC, are often characterized by aerobic glycolysis, also known as the Warburg effect ( Cao et al, 2020 ). However, studies on the Warburg effect often focus on hepatocellular carcinoma or breast cancer ( Li et al, 2018 ; Zheng et al, 2019 ; Huang et al, 2021 ; Zuo et al, 2021 ). Few studies on the Warburg effect in LUSC have been reported ( Wang et al, 2018 ; Hoang et al, 2019 ; Cao et al, 2020 ; Woźniak et al, 2021 ).…”

Exploration of spatial heterogeneity of tumor microenvironment in nasopharyngeal carcinoma via transcriptional digital spatial profiling

“…However, only MDH1 expression was associated with poor prognosis in patients diagnosed with NSCLC 15 , 16 . MDH1 is predicted to be a prognostic marker of lung squamous cell carcinoma (LUSC) based on multivariate Cox regression analysis 17 . In addition, the frequency of MDH1 mutations in LUSC is 5% in the cBioPortal database 17 .…”

“…MDH1 is predicted to be a prognostic marker of lung squamous cell carcinoma (LUSC) based on multivariate Cox regression analysis 17 . In addition, the frequency of MDH1 mutations in LUSC is 5% in the cBioPortal database 17 . SLC8A1 downstream intergenic region ALK fusion was detected in patients with advanced lung adenocarcinoma 18 .…”