Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Xiangya Hospital, Central South University, Changsha 410008, China.
Aging (Albany NY). 2022 Jul 30;14(14):5946-5958. doi: 10.18632/aging.204195.
Receptor interacting protein kinases (RIPKs) are a family of serine/threonine kinases which are supposed to regulate tumor generation and progression. Rare study illustrates the roles and functions of RIPKs family in lung adenocarcinoma (LUAD) comprehensively. Our results indicated that the expression of RIPK2 higher in LUAD patients while RIPK5 (encoded by gene DSTYK) expression was lower. Only RIPK2 had a strong correlation with pathological stage in LUAD patients. Kaplan-Meier plotter revealed that LUAD patients with low RIPK2 or RIPK3 level showed better overall survival (OS), but worse when LUAD patients with high RIPK5. Further, lower expression of RIPK2 and higher expression of RIPK1, RIPK4 and RIPK5 prompted a longer disease free survival (DFS). Genetic alterations based on cBioPortal revealing 16% alteration rates of RIPK2, as well as RIPK5. We also found that the functions of RIPKs family were linked to cellular senescence, protein serine/threonine kinase activity, apoptosis process et al. TIMER database indicated that the RIPKs family members had distinct relationships with the infiltration of six types of immune cells (macrophages, neutrophils, CD8+ T-cells, B-cells, CD4+ T-cells and dendritic cells). Moreover, RIPK2 could be observed as an independent prognostic factor with Cox proportional hazard model analysis. DiseaseMeth databases revealed that the global methylation levels of RIPK2 increased in LUAD patients. Thus, the findings above will enhance the understanding of RIPKs family in LUAD pathology and progression, providing novel insights into RIPKs-core therapy for LUAD patients.
受体相互作用蛋白激酶 (RIPKs) 是一组丝氨酸/苏氨酸激酶，被认为可以调节肿瘤的发生和进展。很少有研究全面阐明 RIPKs 家族在肺腺癌 (LUAD) 中的作用和功能。我们的研究结果表明，RIPK2 在 LUAD 患者中的表达水平较高，而 RIPK5（由基因 DSTYK 编码）的表达水平较低。只有 RIPK2 与 LUAD 患者的病理分期有很强的相关性。Kaplan-Meier 绘图器显示，LUAD 患者中 RIPK2 或 RIPK3 水平较低的患者总生存期 (OS) 更好，但 RIPK5 水平较高的患者则更差。此外，RIPK2 表达水平降低和 RIPK1、RIPK4 和 RIPK5 表达水平升高提示无病生存期 (DFS) 更长。基于 cBioPortal 的遗传改变显示 RIPK2 的改变率为 16%，RIPK5 也是如此。我们还发现 RIPKs 家族的功能与细胞衰老、丝氨酸/苏氨酸蛋白激酶活性、细胞凋亡过程等有关。TIMER 数据库表明 RIPKs 家族成员与六种类型免疫细胞（巨噬细胞、中性粒细胞、CD8+T 细胞、B 细胞、CD4+T 细胞和树突状细胞）的浸润有明显的关系。此外，通过 Cox 比例风险模型分析，RIPK2 可作为一个独立的预后因素。DiseaseMeth 数据库显示，LUAD 患者中 RIPK2 的整体甲基化水平升高。因此，上述发现将增强我们对 RIPKs 家族在 LUAD 发病机制和进展中的认识，为 LUAD 患者的 RIPKs 核心治疗提供新的见解。
