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.