RIPK2 is an unfavorable prognosis marker and a potential therapeutic target in human kidney renal clear cell carcinoma.
RIPK2 is an unfavorable prognosis marker and a potential therapeutic target in human kidney renal clear cell carcinoma.
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RIPK2是人肾肾透明细胞癌的不良预后标志物和潜在的治疗靶点
DOI：
10.18632/aging.202808
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发表时间：
2021-03-31
期刊：
影响因子：
--
通讯作者：
Bo W
中科院分区：
文献类型：
--
作者：
Li D;Tang L;Liu B;Xu S;Jin M;Bo W
受体相互作用丝氨酸/苏氨酸激酶2（RIPK 2）位于染色体8 q21上，并且编码含有C-末端胱天蛋白酶激活和募集结构域（CARD）的蛋白质，其是先天性和适应性免疫途径中的信号复合物的组分。为探讨RIPK 2在肾透明细胞癌（KIRC）患者预后评估和靶向治疗中的价值，我们对526例KIRC患者的基因组进行了分析。我们的结果表明，与正常样本相比，RIPK 2在KIRC肿瘤样本中上调。进行考克斯回归以计算RIPK 2表达作为总体生存的不利预后特征的风险比。RIPK 2的表达与高危患者的临床分期、转移特征呈正相关。RIPK 2的上调与KIRC患者队列中的各种免疫信号通路失调以及免疫表型变化密切相关。此外，通过shRNA介导的敲低或抑制剂抑制RIPK 2活性显著降低肾癌细胞活力、体外迁移和体内肿瘤生长受损。总之，RIPK 2表达升高表明KIRC患者预后较差，可作为肾癌潜在的预后生物标志物和治疗靶点。
Receptor Interacting Serine/Threonine Kinase 2 (RIPK2) is located on chromosome 8q21 and encodes a protein containing a C-terminal caspase activation and recruitment domain (CARD), which is a component of signaling complexes in both the innate and adaptive immune pathways. To estimate the value of RIPK2 in evaluating the prognosis and guiding the targeted therapy for patients with kidney renal clear cell carcinoma (KIRC), we analyzed total 526 KIRC samples from The Cancer Genome Atlas (TCGA) database. Our result showed that RIPK2 was upregulated in KIRC tumor samples compared with normal samples. Cox regression was performed to calculate the hazard ratio of RIPK2 expression as an unfavorable prognosis feature for overall survival. Moreover, RIPK2 expression was positively correlated to the high-risk clinical stage, and metastasis features. The upregulation of RIPK2 was strongly correlated with various immune signaling pathway dysregulations as well as immune phenotypes changes in KIRC patient’s cohort. In addition, inhibition of RIPK2 activity by either shRNA-mediated knockdown or inhibitor significantly reduced kidney cancer cell viability, trans-migration in vitro, and impaired tumor growth in vivo. In conclusion, elevated RIPK2 expression indicates a worse prognosis for KIRC patients and could serve as a potential prognostic biomarker and therapeutic target in kidney cancer.
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影响因子：
16.6
作者：
Nachbur, Ueli;Stafford, Che A.;Silke, John
通讯作者：
Silke, John
影响因子：
30.8
作者：
Chia, Jer-Ming;Song, Chi;Ware, Doreen
通讯作者：
Ware, Doreen
影响因子：
3.7
作者：
Zhang, Peng;Zheng, Pan;Liu, Yang
通讯作者：
Liu, Yang
DOI：
10.1186/bcr3629
发表时间：
2014-03-19
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Singel SM;Batten K;Cornelius C;Jia G;Fasciani G;Barron SL;Wright WE;Shay JW
通讯作者：
Shay JW
影响因子：
11.2
作者：
Li T;Fan J;Wang B;Traugh N;Chen Q;Liu JS;Li B;Liu XS
通讯作者：
Liu XS