BackgroundThe GSDM family includes six members, GSDMA, GSDMB, GSDMC, GSDMD, GSDME (DFNA5), and PJVK (Pejvakin, DFNB59), which can induce pyroptosis, thereby regulating the tumorigenesis of various cancers. However, the clinical characteristics and role of the GSDM family in LUAD are not well understood.MethodsIn this study, several important bioinformatics databases were used to integrate the analysis of the expression, prognostic value, and immune infiltration of GSDMs in LUAD. These databases include UALCAN, DiseaseMeth, GEPIA, THPA, cBioPortal, TIMER, WebGestalt, STRING database, and Cytoscape.ResultsThe findings from the UALCAN database revealed that the expression of all six GSDMs based on the tumor stage in LUAD was increased (particularly GSDMD). Our IHC results verified it. Additionally, the DiseaseMeth database showed that the methylation levels of GSDMA, GSDMB, GSDMC, and GSDMD were decreased. The expression of six GSDMs was related to shorter overall survival in patients with LUAD, according to the GEPIA database. The cBioPortal database was further used to explore the alteration rate and correlated genes in LUAD. Subsequently, these genes were subjected to functional enrichment and protein-protein interaction network analyses. We identified that the GSDM family regulate several signaling pathways, including immune-associated signaling pathways. According to tumor-infiltrating immune cell analysis from the TIMER database, GSDM family members are associated with the infiltration of important immune cells and their signature markers.ConclusionsGSDM family may be prognostic markers and novel strategies for the treatment of LUAD.

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Background The sirtuins (SIRTs) family is a nicotinamide adenine dinucleotide (NAD+) family of dependent deacetylases, which includes SIRT1-7. This family is related to the development and progression of various tumors. However, a comprehensive analysis of the role of SIRTs in clear cell renal cell carcinoma (ccRCC) is still lacking, and there are few reports on the inhibitory role of SIRT5 in ccRCC. Methods We used immunohistochemical analysis, and several bioinformatic databases to perform an integrated analysis of the expression and prognostic value of SIRT5 and other SIRT family members in ccRCC along with the associated immune cell infiltration. These databases include TIMER, THPA, cell culture, UALCAN, cBioPortal, WebGestalt, Metascape, DiseaseMeth, STRING database, and Cytoscape. Results The protein expression of SIRT1, 2, 3, 6, and 7 were upregulated in ccRCC for the Human Protein Atlas database, whereas the expression of SIRT4 and SIRT5 was decreased. The expression based on tumor stage, and grade followed a similar trend. Kaplan–Meier analysis showed that high SIRT4 and SIRT5 expression was positively related to better overall survival (OS), whereas SIRT6 and SIRT7 expression was positively related to worse OS. Further, high SIRT3 expression was related to worse relapse-free survival (RFS), whereas high SIRT5 expression was related to better RFS. To explore the mechanism underlying the function of SIRTs in ccRCC, we also used several databases to perform the functional enrichment analysis and explore the relationship between infiltrating immune cells and seven SIRT family members in ccRCC. The results showed that several SIRT family members, and particularly SIRT5, are correlated with the infiltration of some important immune cells. The protein expression of SIRT5 was significantly lower in tumor tissue compared to normal tissue and was negatively related to the age of the patient ccRCC individual tumor stages, and grades. In human ccRCC samples, strong IHC staining expression of SIRT5 was displayed in adjacent normal tissue than in tumor tissues. Conclusion SIRT5 may be a prognostic marker and a novel strategy for the treatment of ccRCC.

Background Mammalian STE20-like kinase 1 (MST1/STK4/KRS2) is a highly conservative serine/threonine kinase, as well as a a core member of the Hippo signaling pathway. STK4 has been reported play important roles in mutiple tumors. However, there has still been no systematic and comprehensive study on the role of the STK4 in ccRCC. Methods In this study, experiments including Immunohistochemistry (IHC), western blot (WB), and quantitative real-time-polymerase chain reaction (RT-PCR) combined with bioinformatics analysis were used to integrate the analysis of the expression, prognostic value, and immune infiltration of STK4 in ccRCC. Results The findings from the TCGA database revealed that the expression of STK4 and its expression based on the tumor stage, tumor grade, and nodal metastasis status in ccRCC was increased. The results of IHC, WB, and RT-PCR further verified it. Additionally, the receiver operating characteristic (ROC) curve was used to clarify the diagnositic value of STK4 in patients with ccRCC. According to the Timer database, we found that the high expression of STK4 has significant (p < 0.001) association with renal cancer (including ccRCC) patients survival, suggesting that STK4 is a reliable prognostic predictors. Then, GSEA was performed to explore the mechanism underlying the functions of STK4 in ccRCC. We found that STK4 may play roles in immunoregulatory interactions. Subsequently, STK4 were subjected to immune infiltration analyses. Results suggested that STK4 may play roles in the development of ccRCC by adjusting immune infiltration by influencing NK and pDCs cell. Conclusions STK4 may be prognostic markers in ccRCC and potential for finding novel strategies for the treatment of patients with ccRCC.