Integrative Analysis of Pyroptosis-Related Prognostic Signature and Immunological Infiltration in Lung Squamous Cell Carcinoma

Abstract

Background Lung cancer is one of leading causes of human health threatening with approximately 2.09 million initially diagnosed cases and 1.76 million deaths worldwide annually. Pyroptosis is a programmed cell death mediated by Gasdermin family proteins. Pyroptosis could suppress the tumor oncogenesis and progression; nevertheless, pyroptosis could promote tumor growth by forming a suitable microenvironment. Methods LASSO Cox regression analysis was performed to construct prognostic pyroptosis-related gene (PRG) signature. A ceRNA was constructed to explore the potential lncRNA-miRNA-mRNA regulatory axis in LUSC. Results The expression of 26 PRGs were increased or decreased in LUSC. We also summarized simple nucleotide variation and copy number variation landscape of PRGs in LUSC. Prognosis analysis suggested a poor overall survival rate in LUSC patients with high expression of IL6, IL1B, ELANE, and CASP6. A pyroptosis-related prognostic signature was developed based on four prognostic PRGs. High-risk score LUSC patients had a poor overall survival rate versus low-risk score patients with an AUC of 0.565, 0.641, and 0.619 in 1-year, 3-year, and 5-year ROC curves, respectively. Moreover, the risk score was correlated with immune infiltration in LUSC. Further analysis revealed that pyroptosis-related prognostic signature was correlated with immune cell infiltration, tumor mutation burden, microsatellite instability, and drug sensitivity. We also constructed a ceRNA network and identified a lncRNA KCNQ1OT1/miR-328-3p/IL1B regulatory axis for LUSC. Conclusion A bioinformatics method was performed to develop a pyroptosis-related prognostic signature containing four genes (IL6, IL1B, ELANE, and CASP4) in LUSC. We also constructed a ceRNA network and identified a lncRNA KCNQ1OT1/miR-328-3p/IL1B regulatory axis for LUSC. Further in vivo and in vitro studies should be conducted to verify these results.