Comprehensive analysis reveals immunosuppressive part of SSRP1 in pan-cancer and its potential funtion in pancreatic cancer

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Abstract

Background Research increasingly showed a correlation between Structure Specific Recognition Protein 1 (SSRP1) and the progression of diverse cancers. Nonetheless, the influences of SSRP1 on pan-cancer remains inadequately understood. Methods Differential expression of SSRP1 at mRNA levels was systematically assessed across 33 cancer types utilizing TCGA, GTEx and GEO datasets. Analysis of SSRP1 protein expression levels was conducted through the UALCAN tool. Extensive bioinformatics analyses on 33 cancer types, encompassing tumor mutational burden, prognostic, methylation, and immune microenvironment analyses, we employed Sangerbox 3.0, PanCanSurvPlot ,TISIDB, TIDE, TISCH2 and CancerSEA platform for comprehensive analysis. To elucidate the spatial distribution and functional relevance of SSRP1, we first performed spatial transcriptomic analysis by querying CROST and SpatialDB. Subsequently, siRNA-mediated knockdown of SSRP1 was conducted in pancreatic cancer cell lines followed by a panel of functional assays to assess its role in tumorigenesis. Results It was observed that SSRP1 expression increased in the majority of tumors acting an essential role in prognosis and diagnosis. There was a strong correlation between terrible clinical outcomes and SSRP1 expression in ACC, LAML, MESO, PAAD and SARC. The association between SSRP1 and tumor heterogeneity, stemness, DNA methyltransferases and Homologous Recombination Repair (HRR) genes were examined. We investigated the relationship between SSRP1 and immune infiltration as well as immunotherapy in pan-cancer. In the analysis of immune microenvironment, SSRP1 was positively correlated with immune supression and Patients exhibiting elevated expression levels of SSRP1 had poor response to immunotherapy. In vitro, the knockdown of SSRP1 inhibited the proliferation, migration and invasion of pancreatic cancer was firstly detected in this study. Conclusion In summary, our research offers a comprehensive analysis of SSRP1's functional mechanisms across various cancers and confirms its role in pancreatic cancer, underscoring its Prognostic and therapeutic potential.

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