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PTBPs:一种泛癌中与免疫调节相关的预后生物标志物。

PTBPs: An immunomodulatory-related prognostic biomarker in pan-cancer.

作者信息

Chen Chen, Shang Anquan, Gao Yuting, Huang Jingjuan, Liu Gege, Cho William C, Li Dong

机构信息

Department of Laboratory Medicine, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.

Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, Hong Kong SAR, China.

出版信息

Front Mol Biosci. 2022 Aug 23;9:968458. doi: 10.3389/fmolb.2022.968458. eCollection 2022.

Abstract

The polypyrimidine tract-binding protein (PTBP) nuclear ribonucleoprotein family of proteins, including PTBP1, PTBP2 and PTBP3, regulate the process of cell proliferation, differentiation, apoptosis and carcinogenesis. PTBPs exhibit oncogenic effects in certain tumors. However, the role of PTBPs in pan-cancer remains unclear. Our study examined the clinical significance and mechanism of PTBPs in pan-cancer. We compared the expression of in paired and unpaired tissue samples from the Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression, Kaplan-Meier curves, and time-dependent receiver operating characteristic (ROC) curves were used to assess the prognostic significance of in pan-cancer. The cBioPortal database also identified genomic abnormalities in . TISIDB, TCGA, and Cellminer were used to investigate the relationship between expression and immune subtypes, immune checkpoint (ICP) genes, tumor mutational burden (TMB), microsatellite instability (MSI), tumor-infiltrating immune cells, and chemosensitivity. cBioPortal was used to search for co-expressing genes in pan-cancer, and GO and KEGG enrichment analyses were performed to search for -related signaling pathways. were shown to be widely upregulated in human tumor tissues. showed good prognostic value in ACC, KIRP, and LGG; in ACC and KICH; and in ACC, LGG, and PAAD, with AUC >0.7. were differentially expressed in tumor immune subtypes and had a strong correlation with tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment (TME). In addition, expressions were related to ICP, TMB, and MSI, suggesting that these three PTBPs may be potential tumor immunotherapeutic targets and predict the efficacy of immunotherapy. Enrichment analysis of co-expressed genes of showed that they may be involved in alternative splicing, cell cycle, cellular senescence, and protein modification. PTBPs are involved in the malignant progression of tumors. , and may be potential biomarkers for prognosis and immunotherapy in pan-cancer and may be novel immunotherapeutic targets.

摘要

多嘧啶序列结合蛋白(PTBP)核核糖核蛋白家族的蛋白质,包括PTBP1、PTBP2和PTBP3,调节细胞增殖、分化、凋亡和致癌过程。PTBPs在某些肿瘤中表现出致癌作用。然而,PTBPs在泛癌中的作用仍不清楚。我们的研究探讨了PTBPs在泛癌中的临床意义和机制。我们比较了来自癌症基因组图谱(TCGA)数据库的配对和未配对组织样本中PTBPs的表达。单因素和多因素Cox回归、Kaplan-Meier曲线和时间依赖性受试者工作特征(ROC)曲线用于评估PTBPs在泛癌中的预后意义。cBioPortal数据库还确定了PTBPs中的基因组异常。利用TISIDB、TCGA和Cellminer研究PTBPs表达与免疫亚型、免疫检查点(ICP)基因、肿瘤突变负担(TMB)、微卫星不稳定性(MSI)、肿瘤浸润免疫细胞和化疗敏感性之间的关系。利用cBioPortal搜索泛癌中PTBPs的共表达基因,并进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析以寻找与PTBPs相关的信号通路。结果显示PTBPs在人类肿瘤组织中广泛上调。PTBP1在肾上腺皮质癌(ACC)、肾嫌色细胞癌(KIRP)和低级别胶质瘤(LGG)中显示出良好的预后价值;PTBP2在ACC和肾透明细胞癌(KICH)中显示出良好的预后价值;PTBP3在ACC、LGG和胰腺癌(PAAD)中显示出良好的预后价值,曲线下面积(AUC)>0.7。PTBPs在肿瘤免疫亚型中差异表达,并且与肿瘤微环境(TME)中的肿瘤浸润淋巴细胞(TILs)密切相关。此外,PTBPs的表达与ICP、TMB和MSI相关,表明这三种PTBPs可能是潜在的肿瘤免疫治疗靶点,并可预测免疫治疗的疗效。对PTBPs共表达基因的富集分析表明,它们可能参与可变剪接、细胞周期、细胞衰老和蛋白质修饰。PTBPs参与肿瘤的恶性进展。PTBP1、PTBP2和PTBP3可能是泛癌预后和免疫治疗的潜在生物标志物,并且可能是新型免疫治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/678d/9531344/feabe4c96a70/fmolb-09-968458-g001.jpg

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