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泛癌分析显示为一种用于预后和免疫治疗的新生物标志物。

Pan-Cancer Analysis Revealed as a New Biomarker for Prognosis and Immunotherapy.

作者信息

Liu Jinhui, Wang Yuanyuan, Yin Jian, Yang Yan, Geng Rui, Zhong Zihang, Ni Senmiao, Liu Wen, Du Mulong, Yu Hao, Bai Jianling

机构信息

Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.

Department of Biostatistics, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, China.

出版信息

J Oncol. 2022 Jan 12;2022:3477148. doi: 10.1155/2022/3477148. eCollection 2022.

Abstract

BACKGROUND

Serine/arginine-rich splicing factor 9 () is one of the members of gene family and related to the tumorigenesis and the progression of tumor. However, whether 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 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 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, expression was upregulated in most cancers, such as BLCA, CHOL, and UCEC, which 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 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.

摘要

背景

富含丝氨酸/精氨酸的剪接因子9(SRSF9)是SRSF基因家族成员之一,与肿瘤发生及进展相关。然而,SRSF9在泛癌中是否起关键作用仍不清楚。

方法

在本研究中,我们使用了诸如癌症基因组图谱(TCGA)、癌细胞系百科全书(CCLE)和基因型-组织表达(GTEx)等公共数据库,分析肿瘤细胞与正常细胞中SRSF9的表达水平。采用生存分析、K-M绘图仪和PrognoScan分析SRSF9对总生存期(OS)、疾病特异性生存期(DSS)、无病间期(DFI)和无进展生存期(PFI)的预后价值。此外,我们运用生物信息学方法以及TISIDB、TIMER和Sangerbox网站,分析SRSF9与临床特征(包括预后结果)、肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)、免疫检查点基因、肿瘤微环境(TME)、免疫浸润细胞、错配修复(MMR)基因、m6A基因、DNA甲基转移酶和新抗原等分子事件之间的相关性。

结果

总体而言,SRSF9在大多数癌症中表达上调,如膀胱癌(BLCA)、胆管癌(CHOL)和子宫内膜癌(UCEC),这与生存期缩短和病情严重进展相关。在结肠癌(COAD)、胃癌(STAD)和子宫内膜癌中,SRSF9表达与TMB和MSI均呈正相关。在乳腺癌(BRCA)、膀胱癌、食管癌(ESCA)、胶质母细胞瘤(GBM)、头颈部鳞状细胞癌(HNSC)、肺鳞状细胞癌(LUSC)、肺腺癌(LUAD)、卵巢癌(OV)、前列腺癌(PRAD)、睾丸生殖细胞肿瘤(TGCT)、甲状腺癌(THCA)和子宫内膜癌中,免疫评分和基质评分均与SRSF9表达呈负相关。在低级别胶质瘤(LGG)中,免疫评分与SRSF9表达呈正相关。除肺鳞状细胞癌外,SRSF9表达在LGG、肾透明细胞癌(KIRC)、肝癌(LIHC)、嗜铬细胞瘤(PCPG)、前列腺癌、皮肤黑色素瘤(SKCM)、甲状腺癌和胸腺瘤中与六种免疫浸润细胞呈显著正相关。在肝癌中,SRSF9与大多数免疫检查点基因高度显著相关。对于新抗原,在某些癌症类型中,SRSF9与新抗原数量之间的相关性显著为正。SRSF9还与MMR基因、m6A基因和DNA甲基转移酶相关。在33种癌症类型中,基因集富集分析(GSEA)表明SRSF9与多种功能和信号通路相关。

结论

这些发现表明,SRSF9可能是多种癌症预后和免疫治疗的新生物标志物。因此,这将有助于为癌症患者提供新的治疗方法,从而改善癌症患者的治疗效果和预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a638/8769850/153a49f5f937/JO2022-3477148.001.jpg

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