Urology Department, First Hospital of Shanxi Medical University, First Clinical Collage of Shanxi Medical University, Shanxi Medical University, Taiyuan 030001, China.
Department of Nephrology, Beijing-Chaoyang Hospital, Beijing 100020, China.
Aging (Albany NY). 2021 Mar 31;13(7):10450-10467. doi: 10.18632/aging.202808.
Serine 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 , and impaired tumor growth . 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.
丝氨酸位于 8q21 染色体上，编码一种含有 C 末端半胱天冬酶激活和募集结构域（CARD）的蛋白质，该结构域是先天和适应性免疫途径中信号复合物的组成部分。为了评估 RIPK2 在评估肾透明细胞癌（KIRC）患者预后和指导靶向治疗中的价值，我们分析了来自癌症基因组图谱（TCGA）数据库的总共 526 个 KIRC 样本。我们的结果表明，与正常样本相比，RIPK2 在 KIRC 肿瘤样本中上调。进行 Cox 回归以计算 RIPK2 表达作为总生存期不良预后特征的风险比。此外，RIPK2 表达与高风险临床分期和转移特征呈正相关。RIPK2 的上调与 KIRC 患者队列中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 RIPK2 活性显著降低了肾癌细胞的活力、迁移，并损害了肿瘤生长。总之，RIPK2 表达升高表明 KIRC 患者的预后更差，可能成为肾癌的潜在预后生物标志物和治疗靶点。
