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鉴定与透明细胞肾细胞癌发生相关的潜在关键基因。

Identification of potential crucial genes associated with carcinogenesis of clear cell renal cell carcinoma.

机构信息

Department of Urinary Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P. R. China.

Hilongjiang Academy of Medical Sciences, Harbin, Heilongjiang, P. R. China.

出版信息

J Cell Biochem. 2018 Jul;119(7):5163-5174. doi: 10.1002/jcb.26543. Epub 2018 Apr 6.

Abstract

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy with high mortality. However, the molecular pathogenesis of ccRCC remains unclear and effective biomarkers for daily practice are still limited. Thus, we aimed to identify the potential crucial genes and pathways associated with carcinogenesis of ccRCC and further analyze the molecular mechanisms implicated in tumorigenesis. In the present study, expression profiles GSE 66270, GSE 53757, GSE 36895, and GSE 76351 were downloaded from GEO database, including 244 matched primary and adjacent normal tissues, furthermore, the level 3 RNAseq dataset (RNAseqV2 RSEM) of KIRC was also downloaded from The Cancer Genome Atlas (TCGA), which consist of 529 ccRCC tumors and 72 normal tissues. Then, differentially expressed genes (DEGs) and pathway enrichment were analyzed by using R software. A total of 129 up- and 123 down-regulated genes were identified, which were aberrantly expressed both in GEO and TCGA data. Second, Gene ontology (GO) analyses revealed that most of the DEGs were significantly enriched in integral component of membrane, extracellular exosome, plasma membrane, cell adhesion, and receptor binding. Signaling pathway analyses indicated that DEGs had common pathways in signal transduction, metabolism, and immune system. Third, hub genes were identified with protein-protein interaction (PPI) network, including PTPRC, TGFB1, EGF, MYC, ITGB2, CTSS, FN1, CCL5, KNG1, and CD86. Additionally, sub-networks analyse was also performed by using MCODE plugin. In conclusion, the novel DEGs and pathways in ccRCC identified in this study may provide new insight into the underlying molecular mechanisms that facilitates RCC carcinogenesis.

摘要

透明细胞肾细胞癌(ccRCC)是一种常见的泌尿生殖系统恶性肿瘤,死亡率较高。然而,ccRCC 的分子发病机制尚不清楚,日常实践中有效的生物标志物仍然有限。因此,我们旨在确定与 ccRCC 发生相关的潜在关键基因和途径,并进一步分析肿瘤发生中涉及的分子机制。在本研究中,从 GEO 数据库中下载了表达谱 GSE66270、GSE53757、GSE36895 和 GSE76351,其中包括 244 对匹配的原发性和相邻正常组织,此外,还从癌症基因组图谱(TCGA)下载了 KIRC 的级别 3 RNAseq 数据集(RNAseqV2 RSEM),其中包含 529 例 ccRCC 肿瘤和 72 例正常组织。然后,使用 R 软件分析差异表达基因(DEGs)和途径富集。在 GEO 和 TCGA 数据中,共鉴定出 129 个上调和 123 个下调基因,这些基因表达异常。其次,基因本体(GO)分析表明,大多数 DEGs 显著富集在膜的整体成分、细胞外外泌体、质膜、细胞粘附和受体结合中。信号通路分析表明,DEGs 在信号转导、代谢和免疫系统中有共同的途径。第三,通过蛋白质-蛋白质相互作用(PPI)网络鉴定了枢纽基因,包括 PTPRC、TGFB1、EGF、MYC、ITGB2、CTSS、FN1、CCL5、KNG1 和 CD86。此外,还使用 MCODE 插件进行了子网分析。总之,本研究中鉴定的 ccRCC 中的新 DEGs 和途径可能为深入了解促进 RCC 癌变的潜在分子机制提供新的见解。

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