Novel pyroptosis-associated genes signature for predicting the prognosis of sarcoma and validation

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.

Sarcoma cases were classified into two subtypes with regards to differentially expressed genes. We established a profile composed of seven genes and classified the sarcoma patients into low- and high-risk groups through least absolute shrinkage and selection operator 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 with low-risk patient group. In addition, functional enrichment, pathway and gene mutation of the two modules were analyzed. Finally, we used qRT-PCR to detect the expression of seven pyroptosis-related genes in tumor cells, and human skeletal muscle cells, compared with human skeletal muscle cells, PODXL2, LRRC17, GABRA3, SCUBE3 and RFLNB genes show high expression levels in tumor cells, while IGHG2 and hepatic leukemia factor show low expression levels in tumor cells.

Our research suggest that pyroptosis is closely associated with sarcoma, and these findings confirm that pyroptosis-associated seven genes have a critical role in sarcoma and are potential prognostic factors for sarcoma.