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Bioinformatic identification of renal cell carcinoma microenvironment-associated biomarkers with therapeutic and prognostic value.
Life Sciences ( IF 6.1 ) Pub Date : 2020-01-08 , DOI: 10.1016/j.lfs.2020.117273
Qingquan Zeng 1 , Weiyi Zhang 2 , Xiaoling Li 3 , Jianqiang Lai 4 , Zuwei Li 5
Affiliation  

Renal cell carcinoma (RCC) is the ninth most prevalent form of malignancy worldwide. The tumor microenvironment significantly affects gene expression in tumor tissues, which subsequently impacts the prognosis of RCC patients. Available datasets such as The Cancer Genome Atlas (TCGA) can be utilized to improve diagnostic methods and search for novel tumor therapeutic targets and prognostic biomarkers. The current study used the ESTIMATE algorithm to explore the immune and stromal components in RCC. Differentially expressed genes (DEGs) were identified by comparing the gene expression patterns in groups with high and low immune/stromal scores. Functional enrichment analysis was conducted and Kaplan-Meier survival curves were plotted to explore the functions of the DEGs in the tumorigenesis, progression, and prognosis of RCC. Our results revealed that immune and stromal scores are associated with specific clinicopathologic variables in RCC. These variables include gender, tumor grade, tumor stage, tumor size, distant metastasis and prognosis. A total of 48 upregulated and 47 downregulated genes were obtained. Functional enrichment analysis demonstrated a correlation between DEGs and the tumor microenvironment, tumor immune response and RCC tumorigenesis. Kaplan-Meier survival curves showed that 43 out of the 48 identified tumor microenvironment related genes are involved in the prognosis of RCC. Three genes, IL10, IGLL5 and POU2AF1, were selected as the hub genes, and their kinase targets were identified as MAPK1 and PPKCA. A positive correlation was obtained between the expression of IL/POU2AF1 and the abundance of six immune cells. Our study provides potential biomarkers for the therapy and prognosis of RCC.

中文翻译:

肾细胞癌微环境相关生物标志物的生物信息学鉴定,具有治疗和预后价值。

肾细胞癌(RCC)是世界范围内第九大最普遍的恶性肿瘤形式。肿瘤微环境显着影响肿瘤组织中的基因表达,继而影响RCC患者的预后。诸如癌症基因组图谱(TCGA)之类的可用数据集可用于改善诊断方法并搜索新型肿瘤治疗靶标和预后生物标志物。当前的研究使用ESTIMATE算法来探索RCC中的免疫和基质成分。通过比较具有高和低免疫/基质得分的组中的基因表达模式来鉴定差异表达基因(DEG)。进行功能富集分析并绘制Kaplan-Meier生存曲线,以探讨DEG在RCC的发生,发展和预后中的功能。我们的结果表明,免疫和基质评分与RCC中特定的临床病理变量有关。这些变量包括性别,肿瘤等级,肿瘤分期,肿瘤大小,远处转移和预后。总共获得了48个上调基因和47个下调基因。功能富集分析表明,DEG与肿瘤微环境,肿瘤免疫反应和RCC肿瘤发生之间存在相关性。Kaplan-Meier生存曲线表明,在48个已鉴定的肿瘤微环境相关基因中,有43个参与了RCC的预后。选择IL10,IGLL5和POU2AF1这三个基因作为中枢基因,并将其激酶靶点鉴定为MAPK1和PPKCA。IL / POU2AF1的表达与六个免疫细胞的丰度之间呈正相关。
更新日期:2020-01-09
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