CDCA3预测肾细胞癌预后不良并影响CD8 T细胞浸润
CDCA3 Predicts Poor Prognosis and Affects CD8 T Cell Infiltration in Renal Cell Carcinoma.
作者信息
Bai Yuanyuan, Liao Shangfan, Yin Zhenjie, You Bingyong, Lu Dongming, Chen Yongmei, Chen Daoxun, Wu Yongyang
机构信息
Department of Urology, Affiliated Sanming First Hospital, Fujian Medical University, Sanming, 365100 Fujian, China.
出版信息
J Oncol. 2022 Sep 28;2022:6343760. doi: 10.1155/2022/6343760. eCollection 2022.
BACKGROUND
Cell division cycle associated 3 (CDCA3) mediates the ubiquitination WEE1 kinase at G2/M phase. However, its contribution to cancer immunity remains uncertain.
METHODS
We first evaluated the effect of CDCA3 on the prognosis of patients with renal cell carcinoma (RCC). The results of bioinformatics analysis were verified by the tissue microarray, immunofluorescence (IF) staining, CCK-8 assay, colony formation, cell cycle, and Western blot.
RESULTS
Bioinformatics analysis predicated CDCA3 was an independent predictor of poor prognosis in RCC and was associated with poor TNM stage and grade. CDCA3 was related to the infiltration of CD8 T cells and Tregs. Tissue microarray demonstrated that CDCA3 was strongly associated with poor prognosis and positively relevant to CD8 T infiltration. In vitro experiments showed that exgenomic interference of CDCA3 could attenuate cellular proliferation, arrest cell cycle, and blockade accumulation of CDK4, Bub3, and Cdc20 in mitosis process.
CONCLUSION
CDCA3 presents as a good biomarker candidate to predict the prognosis of RCC patients and potentiates the immune tumor microenvironment (TME) of RCC.
背景
细胞分裂周期相关蛋白3（CDCA3）在G2/M期介导WEE1激酶的泛素化。然而，其对癌症免疫的作用仍不确定。
方法
我们首先评估了CDCA3对肾细胞癌（RCC）患者预后的影响。通过组织芯片、免疫荧光（IF）染色、CCK-8检测、集落形成、细胞周期分析和蛋白质免疫印迹法验证了生物信息学分析的结果。
结果
生物信息学分析预测CDCA3是RCC患者预后不良的独立预测因子，且与不良的TNM分期和分级相关。CDCA3与CD8 T细胞和调节性T细胞（Tregs）的浸润有关。组织芯片显示CDCA3与预后不良密切相关，且与CD8 T细胞浸润呈正相关。体外实验表明，对CDCA3进行外基因组干扰可减弱细胞增殖、使细胞周期停滞，并阻断有丝分裂过程中CDK4、Bub3和Cdc20的积累。
结论
CDCA3是预测RCC患者预后的良好生物标志物候选物，并增强了RCC的免疫肿瘤微环境（TME）。
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