Pyroptosis-Related Gene Model Predicts Prognosis and Immune Microenvironment for Non-Small-Cell Lung Cancer

Abstract

Non-small-cell lung cancer (NSCLC) has a high incidence and mortality worldwide. Moreover, it needs more accurate means for predicting prognosis and treatments. Pyroptosis is a novel form of cell death about inflammation which was highly related to the occurrence and development of tumors. Despite having some studies about pyroptosis-related genes (PRGs) and cancer, the correlation has not been explored enough between PRGs and immune in NSCLC. In this study, we constructed a PRG model by WGCNA to access the prognosis value PRGs have. The testing cohort ( n = 464 ) with four datasets from the GEO database conducted a survival analysis to confirm the stability of the prognostic model. The risk score and age are examined as independent prognostic factors. Based on the PRGs, we found multiple pathways enriched in immune in NSCLC. Separating samples into three subtypes by consensus cluster analysis, Cluster 3 was identified as immune-inflamed phenotype with an optimistic prognostic outcome. A three-gene PRG signature (BNIP3, CASP9, and CAPN1) was identified, and BNIP3 was identified as the core gene. Knockdown of BNIP3 significantly inhibited the growth of H358 cells and induced pyroptosis. In conclusion, the model construction based on PRGs provides novel insights into the prediction of NSCLC prognosis, and BNIP3 can serve as a diagnostic biomarker for NSCLC.

Both In Situ and Circulating SLC3A2 Could Be Used as Prognostic Markers for Human Lung Squamous Cell Carcinoma and Lung Adenocarcinoma

“…Primary bronchogenic carcinoma is a malignant tumor that originates from the trachea, bronchus, and lung [ 1 , 2 , 3 ]. Lung cancer is a bronchogenic cancer, examples of which include lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), small-cell carcinoma, and large-cell carcinoma [ 4 , 5 , 6 ]. Lung cancer has a high incidence and mortality worldwide [ 7 ].…”

Probing the Potential of Defense Response-Associated Genes for Predicting the Progression, Prognosis, and Immune Microenvironment of Osteosarcoma

“…Among the three identified genes, BNIP3 has been reported to have an association with osteosarcoma, ovarian cancer, breast cancer, and melanoma prognosis [ 28 , 29 , 30 , 31 ], and BNIP3 is pro-apoptotic in most studies [ 32 ], although there are still some studies indicating that BNIP3 can inhibit apoptosis in tumor cells [ 33 , 34 , 35 ]. Burton et al [ 35 ] reported that nuclear BNIP3 acts as a transcriptional repressor by binding to the promoter region of the AIF gene, thereby preventing apoptosis of glioma cells.…”

“…Burton et al [ 35 ] reported that nuclear BNIP3 acts as a transcriptional repressor by binding to the promoter region of the AIF gene, thereby preventing apoptosis of glioma cells. Luo et al [ 33 ] indicated that knockdown of BNIP3 significantly increased the apoptosis rate of lung cancer cells, and low expression levels of BNIP3 could increase the infiltration of immune cells and improve the prognosis of lung cancer patients. Moreover, the role of BNIP3 in various tumors is inconsistent.…”