Comprehensive analysis prediction prognosis and immune therapy value of angiogenesis-associated genes in kidney renal clear cell carcinoma

Abstract

Abstract Background:Kidney renal clear cell carcinoma (KIRC) is a highly vascularized and immunogenic tumor that has a high percentage of recurrence and a poor prognosis. Anti-angiogenesis therapies and immunotherapy are critical options to treat KIRC. However, the role of angiogenesis-associated genes (AAGs) in renal cell carcinoma tumorigenesis, prognosis prediction, the influence of the tumor microenvironment (TME) and the response to immunotherapy remains unknown. Identifying potential prognostic markers based on AAGs of KIRC may provide information for the early detection of recurrence and treatment. Methods: We investigated the expression profiles of 36 AAGs in 536 KIRC patients, including 536 tumors and 72 adjacent nontumor tissues downloaded fromThe Cancer Genome Atlas (TCGA) database. We determined two different clusters based on AAG expression patterns and comprehensively identified the correlation between angiogenesis and patient risk, overall survival, and immune cell proportion in the TME. Next, we assessed the AAG score in different AAG clusters and confirmed the predictive ability in KIRC patients by a risk score model. Finally, we evaluatedthe IC50 of 12 chemotherapy and targeted drugs in different AAG score groups. Results: We explored the expression levels, CNVs, and mutations of 36 AAGs in KIRC and observed that fifteen differentially expressed genes and VEGFA, TIMP1, VCAN and POSTN were hub genes. Different AAG clusters were divided by theexpression profiles of AAGs, and the survival analysis indicated that the low AAG score and low-risk group demonstrated superior overall survival (OS). We analyzed the correlation between angiogenesis and the TME and found that TME scores in the high AAG score group were higher than those in the low AAG score group. The two clusters had an abundance of metabolic-associated pathways. Next, the clinical viability and OS prediction ability of the AAG score in KIRC patients wereconfirmed by a highly reliable nomogram. Furthermore, different TMB subgroups combined with the AAG_score showed that the low-TMB+low-risk group had greater OS. Additionally, the AAG_score was markedly correlated with chemotherapy and target drug susceptibility. Conclusion: Our results reveal that as a clinical prognostic signature, AAGs play a significant predictive role in KIRC. The relationship between AAGs and the TME should provide more potent combination therapy options for KIRC patients.