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基于33种肿瘤中表达情况的泛癌分析及其在预后和肿瘤免疫中的潜在价值

Pan-Cancer Analysis Based on Expression With Potential Value in Prognosis and Tumor Immunity in 33 Tumors.

作者信息

Zhang Yajing, Wang Senyu, Han Songtao, Feng Yangchun

机构信息

Clinical Laboratory Center, Cancer Hospital Affiliated to Xinjiang Medical University, Xinjiang, China.

Xinjiang Key Laboratory of Oncology, Cancer Hospital Affiliated to Xinjiang Medical University, Xinjiang, China.

出版信息

Front Oncol. 2022 Mar 14;12:844794. doi: 10.3389/fonc.2022.844794. eCollection 2022.

Abstract

BACKGROUND

Erythropoietin receptor (EPOR), a member of the cytokine class I receptor family, mediates erythropoietin (EPO)-induced erythroblast proliferation and differentiation, but its significance goes beyond that. The expression and prognosis of in cancer remain unclear.

METHODS

This study intended to perform a pan-cancer analysis of by bioinformatics methods. Several databases such as GTEx, TCGA, CCLE, and others were used to explore the overall situation of expression, and the correlation of expression with prognosis, microRNAs (miRNAs), immune infiltration, tumor microenvironment, immune checkpoint genes, chemokines, tumor mutation burden (TMB), microsatellite instability (MSI), methyltransferases, and DNA mismatch repair (MMR) genes in 33 tumors was analyzed. In addition, we compared the promoter methylation levels of in cancer tissues with those in normal tissues and performed protein-protein interaction network, gene-disease network, and genetic alteration analyses of , and finally enrichment analysis of EPOR-interacting proteins, co-expressed genes, and differentially expressed genes.

RESULTS

The TCGA database showed that expression was upregulated in BLCA, CHOL, HNSC, KIRC, LIHC, STAD, and THCA and downregulated in LUAD and LUSC. After combining the GTEx database, expression was found to be downregulated in 18 cancer tissues and upregulated in 6 cancer tissues. The CCLE database showed that expression was highest in LAML cell lines and lowest in HNSC cell lines. Survival analysis showed that high expression was positively correlated with OS in LUAD and PAAD and negatively correlated with OS in COAD, KIRC, and MESO. Moreover, had a good prognostic ability for COAD, LUAD, MESO, and PAAD and also influenced progression-free survival, disease-specific survival, disease-free survival, and progression-free interval in specific tumors. Further, was found to play a non-negligible role in tumor immunity, and a correlation of with miRNAs, TMB, MSI, and MMR genes and methyltransferases was confirmed to some extent. In addition, the enrichment analysis revealed that is involved in multiple cancer-related pathways.

CONCLUSION

The general situation of expression in cancer provided a valuable clinical reference. may be target gene of hsa-miR-575, etc. A pan-cancer analysis of panoramic schema revealed that EPOR not only may play an important role in mediating EPO-induced erythroblast proliferation and differentiation but also has potential value in tumor immunity and is expected to be a prognostic marker for specific cancers.

摘要

背景

促红细胞生成素受体(EPOR)是细胞因子I类受体家族的成员,介导促红细胞生成素(EPO)诱导的成红细胞增殖和分化,但其意义不止于此。其在癌症中的表达及预后仍不明确。

方法

本研究旨在通过生物信息学方法对EPOR进行泛癌分析。使用了GTEx、TCGA、CCLE等多个数据库来探究EPOR表达的整体情况,并分析了EPOR表达与33种肿瘤的预后、微小RNA(miRNA)、免疫浸润、肿瘤微环境、免疫检查点基因、趋化因子、肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)、甲基转移酶和DNA错配修复(MMR)基因的相关性。此外,我们比较了癌组织和正常组织中EPOR的启动子甲基化水平,并对EPOR进行了蛋白质-蛋白质相互作用网络、基因-疾病网络和基因改变分析,最后对EPOR相互作用蛋白、共表达基因和差异表达基因进行了富集分析。

结果

TCGA数据库显示,EPOR在膀胱尿路上皮癌(BLCA)、胆管癌(CHOL)、头颈部鳞状细胞癌(HNSC)、肾透明细胞癌(KIRC)、肝内胆管癌(LIHC)、胃腺癌(STAD)和甲状腺癌(THCA)中表达上调,在肺腺癌(LUAD)和肺鳞状细胞癌(LUSC)中表达下调。结合GTEx数据库后,发现EPOR在18种癌组织中表达下调,在6种癌组织中表达上调。CCLE数据库显示,EPOR在急性髓系白血病(LAML)细胞系中表达最高,在HNSC细胞系中表达最低。生存分析表明,高EPOR表达与LUAD和胰腺腺癌(PAAD)的总生存期(OS)呈正相关,与结肠腺癌(COAD)、KIRC和间皮瘤(MESO)的OS呈负相关。此外,EPOR对COAD/LUAD/MESO及PAAD具有良好的预后预测能力,且对特定肿瘤的无进展生存期、疾病特异性生存期、无病生存期和无进展间期也有影响。此外,发现EPOR在肿瘤免疫中发挥着不可忽视的作用,并且在一定程度上证实了EPOR与miRNA、TMB、MSI和MMR基因以及甲基转移酶之间的相关性。此外,富集分析显示EPOR参与多种癌症相关途径。

结论

癌症中EPOR表达的总体情况提供了有价值的临床参考。EPOR可能是hsa-miR-575等的靶基因。全景模式的泛癌分析表明,EPOR不仅可能在介导EPO诱导的成红细胞增殖和分化中发挥重要作用,而且在肿瘤免疫中具有潜在价值,有望成为特定癌症的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/809e/8963997/cf8126f13411/fonc-12-844794-g001.jpg

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