A Novel Pyroptosis-Related Gene Signature for Early-Stage Lung Squamous Cell Carcinoma

Xiaoyan Li; Jie He

doi:10.2147/IJGM.S331975

A Novel Pyroptosis-Related Gene Signature for Early-Stage Lung Squamous Cell Carcinoma

Int J Gen Med. 2021 Oct 5:14:6439-6453. doi: 10.2147/IJGM.S331975. eCollection 2021.

Authors

Xiaoyan Li^{1

2}, Jie He^{1

3}

Affiliations

¹ Clinical Medical College of Chengdu Medical College, Chengdu, Sichuan, 610500, People's Republic of China.
² Department of Endocrinology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, People's Republic of China.
³ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, People's Republic of China.

Abstract

Background: Diagnosis of early stage lung squamous cell carcinoma (LUSC) has improved; however, a comprehensive analysis of prognostic signatures is needed.

Purpose: To identify, establish, and validate a signature model based on pyroptosis-related genes for prognostic predictions of early stage LUSC.

Patients and methods: Two independent cohorts were included. RNA-seq transcriptome data from patients with early stage LUSC were obtained from The Cancer Genome Atlas (TCGA) database. Thirty-three pyroptosis-related genes were analyzed between early stage LUSC and normal lung tissues. Cox regression analysis, random survival forest, and least absolute shrinkage and selection operator algorithms established a three-gene signature. Kaplan-Meier survival and receiver-operating characteristic curves assessed the prognostic efficacy of the model. Single-sample gene set enrichment analysis (ssGSEA) assessed the relationship between pyroptosis and immune cells. Patients with early stage LUSC from the GSE74777 dataset were used for validation. Pyroptosis-related genes were verified by RT-qPCR and Western blotting.

Results: Twenty-three differentially expressed pyroptosis-related genes were identified in the LUSC and adjacent normal tissues. Three differentially expressed pyroptosis-related genes were identified as hub genes in early stage LUSC. Patients with early stage LUSC in the TCGA cohort were classified into low- and high-risk subgroups according to the risk score. Overall survival (OS) was significantly short in the high-risk subgroup versus the low-risk subgroup. A similar result was found for the GSE74777 dataset. ssGSEA of immune cells and immune-related pathways between the low- and high-risk subgroups may explain the different OS for patients with early-stage LUSC. IL-6 expression was upregulated, which was inconsistent with the bioinformatic analysis. NOD1 and CASP4 were downregulated in LUSC (all P < 0.05) versus normal lung tissues.

Conclusion: Differentially expressed pyroptosis-related genes may be involved in early stage LUSC. Pyroptosis-related genes are important in tumor immunity and may be potential prognostic predictors for early stage LUSC.

Keywords: early-stage lung squamous cell carcinoma; immunotherapy; prognosis; pyroptosis; tumor microenvironment.

Grants and funding

There is no funding to report.