Novel pyroptosis-associated genes signature for predicting the prognosis of Sarcoma

Abstract Background Sarcoma is a rare mesenchymal malignant tumor. Recently, pyroptosis has been reported to be a mode of programmed cell death. Nonetheless, levels of pyroptosis-associated genes in sarcoma and its relevance to prognostic outcomes are yet to be elucidated. Results We established 33 pyroptosis regulatory genes in sarcoma. Sarcoma cases were classified into two subtypes with regards to differentially expressed genes (DEGs). We constructed a polygenic profile using The Cancer Genome Atlas (TCGA) cohort to assess the prognostic significance of pyroptosis-associated genes for survival. We established a profile composed of 7 genes and classified the sarcoma patients into low- and high-risk groups throughleast absolute shrinkage and selection operator (LASSO) Cox regression. Survival rate of low-risk sarcoma patients was markedly higher, relative to high-risk group (P < 0.001). In combination with clinical features, the risk score was established to be an independent predictive factor for OS of sarcoma patients. Chemotherapeutic Drug Sensitivity response analysis found 65 drugs with higher drug sensitivity in low-risk, than in high-risk group and 14 drugs with higher drug sensitivity in the high-risk patient group, compared to low-risk patient group. Consequently, Gene ontology (GO), Kyoto Encylopedia of Genes and Genomes (KEGG), immune responses and mutations analyses were used to investigate the reasons for the result, which indicated that immune cells infiltration, especially T cell infiltration, and mutations in certain genes, such as TP53 and RB1, may be responsible for poor survival in high-risk patient group. Conclusions our research suggest that pyroptosis is closely associated with Sarcoma, and these findings confirm that pyroptosis-associated seven genes (IGHG2, PODXL2, LRRC17, GABRA3, SCUBE3, HLF, RFLNB) have a critical role in sarcoma and are potential prognostic factors for sarcoma.