摘要： 目的 探讨肿瘤坏死因子α诱导蛋白2(TNFAIP2) 在肾透明细胞癌(ccRCC) 中的表达情况及其临床意义。方法 通过TIMER2.0、癌症基因组图谱(TCGA)、ONCOMINE和UALCAN数据库, 分析TNFAIP2 mRNA在正常肾脏和ccRCC组织中的表达差异, 及其与临床指标和免疫细胞丰度的相关性; 利用Kaplan-Meier曲线数据库分析预后情况。采用Western blotting检测人肾脏正常细胞系HK-2和人肾癌细胞系786-O、ACHN中TNFAIP2的表达, 并应用实时PCR在24个配对的肾癌组织与癌旁肾脏正常组织样本中检测TNFAIP2的表达量。结果 公共数据库分析结果显示,TNFAIP2在ccRCC组织中异常高表达(P < 0.001), 且TNFAIP2的高表达与肿瘤的分期、分级、淋巴结转移、免疫细胞Th1和Treg丰度密切相关(P < 0.001); Kaplan-Meier曲线分析表明TNFAIP2表达与患者的预后有关, 其高表达提示病情恶化及总生存期缩短(P < 0.001);受试者操作特征曲线显示TNFAIP2表达可用于评估患者的诊断预测效率(曲线下面积=0.814)。体外细胞系实验结果显示, 肾癌786-O、ACHN细胞中TNFAIP2表达水平均高于人肾脏正常细胞系HK-2;TNFAIP2 mRNA在ccRCC组织中的平均表达量显著高于正常组织。结论 TNFAIP2在ccRCC中高表达, 且与预后有关, 可作为ccRCC诊断和预后的生物标志物, 为肾癌的靶向治疗提供新方向。

基于公共数据库分析TNFAIP2在肾透明细胞癌中的表达及临床意义

薛东炜, 李明山, 刘嘉, 祝兴旺

中国医科大学附属第四医院泌尿外科, 沈阳 110032

收稿日期:2022-05-09出版日期:2022-08-30发布日期:2022-07-19
通讯作者:薛东炜E-mail:cmu4h-xdw@126.com
作者简介:薛东炜（1973-），男，副主任医师，博士.
基金资助:辽宁省自然科学基金（2020-MS-05）


关键词: 肾透明细胞癌, 癌症基因组图谱, 肿瘤坏死因子α诱导蛋白2, 预后
Abstract: Objective To explore the expression and clinical significance of tumor necrosis factor-α-induced protein 2(TNFAIP2) in the prognosis of clear cell renal cell carcinoma(ccRCC). Methods We analyzed the differential expression of TNFAIP2 mRNA in normal kidney tissue and ccRCC tissues by using TIMER2.0, TCGA, ONCOMINE, and UALCAN databases, and its correlation with clinical indicators and immune cell abundance. Kaplan-Meier curves were used to analyze patient prognosis. Western blotting was used to detect the expression of TNFAIP2 in normal human kidney cell line, HK-2, and human renal cancer cell lines, 786-O and ACHN. Subsequently, cell line results were verified by assessing the TNFAIP2 mRNA expression using RT-PCR in 24 pairs of tissue samples, obtained from matched cancerous and normal patients. Results The sequencing analysis using public databases showed that TNFAIP2 was abnormally highly expressed in ccRCC tissues(P < 0.001). The high expression of TNFAIP2 was closely related to tumor stage, grade, lymph node metastasis, immune cell Th1, and Treg abundance(P < 0.001, each). Kaplan-Meier curve analysis showed that the expression of TNFAIP2 was related to the prognosis of cancer patients. High expression levels of TNFAIP2 indicated progression of the disease and reduced patient survival(P < 0.001). The receiver operating characteristic curve analysis demonstrated that the predictive efficiency of TNFAIP2 expression can be used to evaluate patient disease progression(AUC=0.814). The in vitro cell line experiments showed that the expression of TNFAIP2 in renal cell carcinoma 786-O and ACHN cells was higher than that in the HK-2 cells. The average expression level of TNFAIP2 mRNA of cancer was significantly higher than that in normal tissues, which further confirmed our cell line results. Conclusion The high expression levels of TNFAIP2 in ccRCC is related to the prognosis of patients. Thus, TNFAIP2 levels may serve as a biomarker for the diagnosis and prognosis of ccRCC, and could provide new directions and strategies for targeted therapy of renal cell carcinoma.
Key words: renal clear cell carcinoma, Cancer Genome Atlas, tumor necrosis factor-α-induced protein 2, prognosis
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