Identification of the key genes and pathways involved in the tumorigenesis and prognosis of kidney renal clear cell carcinoma
Identification of the key genes and pathways involved in the tumorigenesis and prognosis of kidney renal clear cell carcinoma
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肾透明细胞癌发生和预后相关关键基因和通路的鉴定
DOI：
10.1038/s41598-020-61162-4
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发表时间：
2020-03-06
影响因子：
4.6
通讯作者：
Liu, Yong
中科院分区：
文献类型：
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作者：
Cui, Hao;Shan, Hongjian;Liu, Yong
肾透明细胞癌（KIRC）是最常见的肾细胞癌（RCC）。然而，由于早期检测和预后预测的生物标志物有限，KIRC 患者的预后通常较差。在这项研究中，我们从包括 26 个肿瘤和 26 个邻近正常组织样本的阵列数据集中分析了 KIRC 中涉及的关键基因和通路。使用 WGCNA 软件包进行加权基因共表达网络分析 (WGCNA)，发现 20 个模块与 KIRC 具有最高相关性。肿瘤样本中上调的基因参与先天免疫反应，而下调的基因则有助于葡萄糖、氨基酸和脂肪酸的细胞分解代谢。此外，通过蛋白质-蛋白质相互作用（PPI）网络与共表达网络相结合来评估关键基因。肿瘤中 AGXT、PTGER3 和 SLC12A3 的表达相对较低，与 KIRC 患者的预后较差相关，而 ALOX5 的较高表达则预示生存率降低。我们的综合分析说明了参与 KIRC 肿瘤发生的中心基因，为预后标志物的开发提供了线索。进一步了解已确定的 KIRC 枢纽基因的功能可以为 KIRC 的分子机制提供深入的见解。
Kidney renal clear cell carcinoma (KIRC) is the most common renal cell carcinoma (RCC). However, patients with KIRC usually have poor prognosis due to limited biomarkers for early detection and prognosis prediction. In this study, we analysed key genes and pathways involved in KIRC from an array dataset including 26 tumour and 26 adjacent normal tissue samples. Weighted gene co-expression network analysis (WGCNA) was performed with the WGCNA package, and 20 modules were characterized as having the highest correlation with KIRC. The upregulated genes in the tumour samples are involved in the innate immune response, whereas the downregulated genes contribute to the cellular catabolism of glucose, amino acids and fatty acids. Furthermore, the key genes were evaluated through a protein-protein interaction (PPI) network combined with a co-expression network. The comparatively lower expression of AGXT, PTGER3 and SLC12A3 in tumours correlates with worse prognosis in KIRC patients, while higher expression of ALOX5 predicts reduced survival. Our integrated analysis illustrated the hub genes involved in KIRC tumorigenesis, shedding light on the development of prognostic markers. Further understanding of the function of the identified KIRC hub genes could provide deep insights into the molecular mechanisms of KIRC.