Expression of pyroptosis-associated genes and construction of prognostic model for thyroid cancer

Lin Guo; Min Yuan; Senhe Jiang; Gang Jin; Ping Li

doi:10.21037/tcr-23-810

Expression of pyroptosis-associated genes and construction of prognostic model for thyroid cancer

Transl Cancer Res. 2023 Dec 31;12(12):3360-3383. doi: 10.21037/tcr-23-810. Epub 2023 Dec 27.

Authors

Lin Guo^#¹, Min Yuan^#¹, Senhe Jiang², Gang Jin¹, Ping Li¹

Affiliations

¹ Department of Nuclear Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
² Department of Otolaryngology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

^# Contributed equally.

Abstract

Background: Thyroid cancer (THCA) is a common endocrine malignancy. This study aimed to explore the expression of pyroptosis-related genes in THCA and establish a prognosis prediction model.

Methods: Differentially expressed pyroptosis-related genes (DEPRGs) were identified in The Cancer Genome Atlas (TCGA) and the Molecular Signatures Database (MSigDB). Subsequently, these genes were subjected to Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A least absolute shrinkage and selection operator (LASSO) regression model was employed to establish a DEPRG signature, and its reliability was validated through survival analysis and receiver operating characteristic (ROC) curves. Patients in TCGA-THCA cohort were stratified into two risk groups. The biological functions of the genes between the two risk groups were assessed through gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). Finally, expression of DEPRGs was validated using datasets from the Gene Expression Omnibus (GEO) and the Human Protein Atlas (HPA) databases.

Results: Six DEPRGs were identified in TCGA dataset. Through LASSO Cox regression analysis, we determined IL6, TP63, NOD1, and BAX to be significant. Kaplan-Meier survival analysis demonstrated that patients with THCA expressing high levels of NOD1 and classified as low-risk individuals exhibited prolonged survival. The multifactorial ROC curves yielded area under the curve (AUC) scores exceeding 0.7 for risk score, age, and T-stage, affirming their significance as independent prognostic factors as determined by multivariate analysis. Additionally, we observed elevated expression levels of BAX and NOD1 in THCA using data derived from the HPA database and the GEO dataset.

Conclusions: We established a novel DEPRG signature for predicting the prognosis of THCA, potentially offering a promising therapeutic marker for THCA treatment.

Keywords: Pyroptosis; gene signature; prognostic model; thyroid cancer (THCA).