Abstract

Background: Anti-angiogenic therapies and immunotherapy are pivotal treatment options for kidney renal clear cell carcinoma (KIRC). However, the role of angiogenesis-associated genes (AAGs) in tumorigenesis of renal cell carcinoma, their potential as prognostic markers, impact on the tumor microenvironment (TME), and response to immunotherapy remain elusive. Identifying promising prognostic indicators based on AAGs in KIRC may facilitate early detection of recurrence and inform treatment strategies.

Methods: We investigated the expression profiles of 36 angiogenesis-associated genes (AAGs) in patients with clear cell renal cell carcinoma (KIRC), including 536 tumor tissues and 72 adjacent non-tumor tissues obtained from The Cancer Genome Atlas (TCGA) database. Two distinct clusters were identified based on AAG expression patterns, and we comprehensively examined the correlation between angiogenesis and patient risk, overall survival, as well as immune cell proportion within the tumor microenvironment (TME). Subsequently, we evaluated the AAG scores within different clusters and validated their predictive ability for KIRC patients using a risk score model. Finally, we assessed the half maximal inhibitory concentration (IC50) values of twelve chemotherapy and targeted drugs across different AAG score groups.

Results: We observed that four differentially expressed genes (VEGFA, TIMP1, VCAN, and POSTN) were identified as hub genes. Survival analysis indicated that both the low AAG score and low-risk groups exhibited superior overall survival (OS). The high AAG score group showed higher TME scores compared to the low AAG score group. These two clusters encompassed a plethora of metabolism-associated pathways. Furthermore, when combined with the AAG_score, different tumor mutation burden (TMB) subgroups demonstrated that the low TMB+low-risk group had a greater OS. Additionally, there was a significant correlation between the AAG_score and susceptibility to chemotherapy and targeted drugs.

Conclusion: Our findings unveil the substantial predictive role of AAGs as a clinical prognostic signature in KIRC. The association between AAGs and TME holds promise for more potent combination therapy options for patients with KIRC.