The RIPK family: expression profile and prognostic value in lung adenocarcinoma.

Abstract

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.