Pan-cancer analysis and experiments with cell lines reveal that the slightly elevated expression of DLGAP5 is involved in clear cell renal cell carcinoma progression
Pan-cancer analysis and experiments with cell lines reveal that the slightly elevated expression of DLGAP5 is involved in clear cell renal cell carcinoma progression
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泛癌分析和细胞系实验表明，DLGAP5 表达的轻微升高参与了透明细胞肾细胞癌的进展
DOI：
10.1016/j.lfs.2021.120056
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发表时间：
2021-10-30
期刊：
影响因子：
6.1
通讯作者：
Zhang, Jing
中科院分区：
文献类型：
--
作者：
Feng, Yun;Li, Fang;Zhang, Jing
目的：盘状大相关蛋白5(DLGAP5)是一种动粒纤维结合蛋白，在多种癌症中起癌蛋白作用。然而，它在包括肾透明细胞癌(CcRCC)在内的泛癌中的表达模式并未被分析。在此，我们旨在评估它在更常见的癌症中的表达，特别是在肾细胞癌中。主要方法：利用基因-组织表达、肿瘤基因组图谱和肿瘤免疫评估资源的数据，分析DLGAP5在正常组织、癌细胞系和癌组织中的表达，以及免疫渗透水平。通过RNAi、Western blotting和细胞学分析对ccRCC细胞系的分析结果进行验证。主要发现：DLGAP5在31种正常组织中低表达，在21种癌细胞系中表达上调，在26种癌症中显著表达，令人惊讶的是，包括ccRCC、DLGAP5在内的肾癌在26种癌症中表达略有升高，但有统计学意义。此外，DLGAP5的高表达与肾细胞癌的免疫浸润程度呈显著正相关。DLGAP5表达上调与肾癌患者的生存概率、临床TNM分期显著相关。实验结果表明，DLGAP5在肾细胞癌组织和细胞系中表达上调，其下调抑制了细胞的存活和增殖，并损害了细胞的迁移和侵袭。意义：DLGAP5在常见癌症中表达升高。然而，它的表达轻微上调与肾细胞癌的进展有关，因此它是肾细胞癌的预后危险因素，但不是一个独立的因素。
Aims: Discs large-associated protein 5 (DLGAP5), a kinetochore fibers-binding protein, functions as a oncoprotein in many cancers. However, its expression patterns in pan-cancer including clear cell renal cell carcinoma (ccRCC) are not analyzed. Herein, we aimed to evaluate its expression in more common cancers, especially in ccRCC. Main methods: Data from Genotype-Tissue Expression, The Cancer Genome Atlas, and Tumor Immune Estimation Resource were used to analyze the DLGAP5 expression in normal tissues, cancer cell lines, and cancer tissues, as well as the immune infiltration levels. The analysis results were verified with ccRCC cell lines via RNAi, western blotting, and the cytological analysis. Key findings: Low DLGAP5 expression in 31 types of normal tissues, the upregulation in 21 cancer cell lines, and the significant elevated expression in 26 types of cancers, were found, Surprisingly, kidney cancer including ccRCC, DLGAP5 exhibited a slightly elevated but statistically significant expression among 26 types of cancers. In addition, elevated DLGAP5 expression was significantly positive correlated with immune infiltration level in ccRCC. The survival probability of some cancers including kidney cancer, clinical TNM stage of ccRCC patients were significantly related to upregulated DLGAP5 expression. The experiments results showed DLGAP5 upregulation in ccRCC tissues and the cell lines, its knockdown inhibited the cells viability and proliferation, and compromised the cells migration and invasion. Significance: Elevated DLGAP5 expression occurred in common cancers. However, its slightly upregulated expression is related with ccRCC progression, it is therefore a prognostic risk factor for ccRCC, but not an independent factor.