Comprehensive analysis illustrating the role of PANoptosis-related genes in lung cancer based on bioinformatic algorithms and experiments

Background: Recently, PANoptosis has aroused the interest of researchers for its role in cancers. However, the studies that investigated PANoptosis in lung cancer are still few. Methods: The public data were mainly collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database. R software was utilized for the analysis of public data. Quantitative real-time (qRT) polymerase chain reaction (PCR) was used to measure the RNA level of FADD. The cell proliferation ability was evaluated using the CCK8, colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. Western blot was used to detect the protein level of specific molecules. Flow cytometry analysis and TUNEL staining were used to evaluate cell apoptosis. Results: In our study, we collected the PANoptosis-related genes from previous studies. Through series analysis, we identified the FADD, an adaptor of PANoptosis and apoptosis, for further analysis. Results showed that FADD is one of the prominent risk factors in lung cancer, mainly localized in nucleoplasm and cytosol. We next performed immune infiltration analysis and biological enrichment to illustrate the underlying cause of FADD in lung cancer. Subsequently, we discovered that the patients with a high level of FADD might respond worse to immunotherapy but better to AICAR, bortezomib, docetaxel, and gemcitabine. In vitro experiments indicated that inhibiting FADD could reduce significantly the ability of cancerous lung cells to proliferate. Meanwhile, we found that the knockdown of FADD promotes the apoptosis and pyroptosis. Ultimately, a prognosis signature was identified based on the FADD-regulated genes, which showed satisfactory prediction efficiency on patients with lung cancer. Conclusion: Our result can provide a novel direction for future studies focused on the role of PANoptosis in lung cancer.