Systematic pan-cancer analysis identifies RBM39 as an immunological and prognostic biomarker.

Systematic pan-cancer analysis identifies RBM39 as an immunological and prognostic biomarker.
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DOI:
10.1111/jcmm.17517
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发表时间:
2022-09
影响因子:
5.3
通讯作者:
--
中科院分区:
医学2区
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--
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RNA结合基序蛋白39(RBM39)被鉴定为剪接因子和转录共激活因子。尽管越来越多的证据表明RBM39在特定恶性肿瘤的发展中起着关键作用,但尚未对RBM39进行系统的泛癌症研究。因此,我们着手研究RBM39在33种不同癌症中的预后意义和推定的免疫活性。基于TCGA和CCLE,GTEX,cBioportal和HPA,我们使用一系列生物信息学方法来探索RBM39的潜在致癌作用,包括分析泛癌物种RBM39的表达,RBM39表达与总生存期(OS),疾病特异性生存期(DSS)和无进展间隔期(PFI)之间的预后关系,RBM39表达与临床表型之间的关系,分析RBM39表达与肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)、DNA甲基化和免疫细胞浸润之间的关系。我们的结果显示RBM39在大多数癌症中过表达。RBM39与不同肿瘤的预后呈正或负相关。RBM39在9种和12种肿瘤中的表达与TMB和MSI相关。此外,RBM39表达与几乎所有肿瘤中的DNA甲基化相关。共筛选出8种肿瘤进行进一步研究,包括BRCA、COAD、HNSC、LIHC、LUSC、SKCM、STAD、UCEC。在筛选的肿瘤中,发现RBM39与大多数免疫细胞的浸润呈负相关。此外,与RBM39表达的相关性因免疫细胞亚型而异。基于RBM39在肿瘤发生和肿瘤免疫中的作用,我们认为它可以作为替代预后标志物。
RNA‐binding Motif Protein39 (RBM39) is identified as a splicing factor and transcription coactivator. Despite mounting evidence that RBM39 plays a critical role in the development of specific malignancies, no systematic pan‐cancer investigation of RBM39 has been conducted. As a result, we set out to investigate RBM39’s prognostic significance and putative immunological activities in 33 different cancers. Based on TCGA and CCLE, GTEx, cBioportal and HPA, we used a series of bioinformatics approaches to explore the potential oncogenic role of RBM39, including analysis of the expression of the pan‐cancer species RBM39, the prognostic relationship between RBM39 expression and overall survival (OS), disease‐specific survival (DSS) and progression‐free interval (PFI), the relationship between RBM39 expression and clinical phenotype, analysis of the relationship between RBM39 expression and tumour mutational burden (TMB), microsatellite instability (MSI), DNA methylation and immune cell infiltration. Our results showed that RBM39 is overexpressed in most cancers. RBM39 was positively or negatively correlated with the prognosis of different tumours. RBM39 expression was associated with TMB and MSI in 9 and 12 cancer types. In addition, RBM39 expression was associated with DNA methylation in almost all tumours. There are eight tumours were screened for further study, including BRCA, COAD, HNSC, LIHC, LUSC, SKCM, STAD, UCEC. In the screed tumours, RBM39 was found to be negatively correlated with the infiltration of most immune cells. In addition, the correlation with RBM39 expression varied by immune cell subtype. Based on RBM39’s role in tumorigenesis and tumour immunity, we suggest it can serve as a surrogate prognostic marker.
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