Abstract
Background Serine/arginine-rich splicing factor 9 (SRSF9) is one of the members of SRSF gene family and related to the tumorigenesis and the progression of tumor. However, whether SRSF9 has a crucial role across pan-cancer is still unknown. Methods In this study, we used public databases, such as The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx), to analyze SRSF9 expression level among tumor and normal cells. Survival analysis, K-M plotter, and PrognoScan were used to analyze the prognosis value of SRSF9, regarding to overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Moreover, we performed the correlation between SRSF9 and clinical characteristics (including the outcome of prognosis), as well as molecular events of tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoint gene, tumor microenvironment (TME), immune infiltrating cells, mismatch repair (MMR) genes, m6A genes, DNA methyltransferases, and neoantigen with bioinformatics methods and TISIDB, TIMER, and Sangerbox websites. Results In general, SRSF9 expression was upregulated in most cancers, such as BLCA, CHOL, and UCEC, which SRSF9 was associated with short survival and severe progression. In COAD, STAD, and UCEC, SRSF9 expression was positively related to both TMB and MSI. In BRCA, BLCA, ESCA, GBM, HNSC, LUSC, LUAD, OV, PRAD, TGCT, THCA, and UCEC, both immune score and stomal score showed a negative relationship with SRSF9 expression. Immune score showed a positive relationship with SRSF9 expression in LGG. SRSF9 expression had a significant and positive correlation with six types of immune infiltration cells in LGG, KIRC, LIHC, PCPG, PRAD, SKCM, THCA, and THYM, except in LUSC. In LIHC, SRSF9 was highly significant correlated with most immune checkpoint genes. For neoantigens, correlation between SRSF9 and the quantity of neoantigens was significantly positive in some cancer types. SRSF9 was also correlated with MMR genes, m6A genes, and DNA methyltransferases. In the 33 cancer types, gene set enrichment analysis (GSEA) demonstrated that SRSF9 was correlated with multiple functions and signaling pathways. Conclusion These findings demonstrated that SRSF9 may be a new biomarker for the prognosis and immunotherapy in various cancers. As a result, it will be beneficial to provide new therapies for cancer patients, thereby improving the treatment and prognosis of cancer patients.
Highlights
SR proteins are a family of proteins participated in RNA splicing [1]. e SR proteins essentially participate in almost every step of the regulation of protein synthesis including mRNA transport, splicing, synthesis of the polypeptide, and formation of the translational initiation complex [2]
Pan-cancer RNA sequencing data, survival data, and clinicopathological characteristics related to 33 cancer types were downloaded from online database UCEC, which was originated from TCGA database [7]. e sequencing data of Serine/arginine-rich splicing factor 9 (SRSF9) were acquired from Genotype-Tissue Expression (GTEx) Project and Broad Institute Cell Line Encyclopedia (CCLE) database to analyze the difference between tumor and adjacent normal tissues
Kaplan–Meier survival analysis was conducted here to discover the differential survival outcomes between two groups, and the use of univariate Cox regression model was to determine the favorable or unfavorable prognosis value of SRSF9, regarding aspects of overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). e K-M analysis was conducted by R package “survminer” and “survival,” and forest plot from Cox regression was realized through R package “survival” and “forestplot.”
Summary
SR proteins (serine/arginine-rich splicing factor, SRSF) are a family of proteins participated in RNA splicing [1]. e SR proteins essentially participate in almost every step of the regulation of protein synthesis including mRNA transport, splicing, synthesis of the polypeptide, and formation of the translational initiation complex [2]. Serine/arginine-rich splicing factor 9 (SRSF9) is one of the members of SRSF gene family and related to the tumorigenesis and the progression of tumor. We performed the correlation between SRSF9 and clinical characteristics (including the outcome of prognosis), as well as molecular events of tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoint gene, tumor microenvironment (TME), immune infiltrating cells, mismatch repair (MMR) genes, m6A genes, DNA methyltransferases, and neoantigen with bioinformatics methods and TISIDB, TIMER, and Sangerbox websites. SRSF9 expression had a significant and positive correlation with six types of immune infiltration cells in LGG, KIRC, LIHC, PCPG, PRAD, SKCM, THCA, and THYM, except in LUSC. In the 33 cancer types, gene set enrichment analysis (GSEA) demonstrated that SRSF9 was correlated with multiple functions and signaling pathways. It will be beneficial to provide new therapies for cancer patients, thereby improving the treatment and prognosis of cancer patients
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