COMPREHENSIVE ANALYSIS PREDICTION PROGNOSIS AND IMMUNE THERAPY VALUE OF ANGIOGENESIS-ASSOCIATED GENES IN KIDNEY RENAL CLEAR CELL CARCINOMA

Abulaiti Maimaitiming^{1, #}, Huerxidan Niyazi^{2, #}, Xiaoyan Dong¹, Yuefen zhang², Ruili Zhang and Ainiwaer Aimudula^{2, *}

¹Department of Urology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China, ²Cancer Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

Background: Anti-angiogenesis therapies and immunotherapy are critical options for the treatment of kidney renal clear cell carcinoma (KIRC). However, the role of angiogenesis-associated genes (AAGs) in renal cell carcinoma tumorigenesis, prognosis prediction, influence of the tumor microenvironment (TME) and response to immunotherapy remains unknown. Identifying potential prognostic markers based on the AAGs of KIRC may provide information for early detection of recurrence and treatment.

Methods: We investigated the expression profiles of 36 AAGs in 536 KIRC patients, including 536 tumor and 72 adjacent non-tumor tissues downloaded from The 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 scores in different AAG clusters and confirmed their predictive ability in patients with KIRC using a risk score model. Finally, we evaluated the IC50 values of 12 chemotherapy and targeted drugs in the different AAG score groups.

Results: We observed that 15 differentially expressed genes (VEGFA, TIMP1, VCAN, and POSTN) were hub genes. Survival analysis indicated that the low AAG score and low-risk groups demonstrated superior overall survival (OS). TME scores in the high AAG score group were higher than those in the low AAG score group. These two clusters contained abundant of metabolism-associated pathways. Furthermore, different Tomor mutation burden (TMB) subgroups combined with the AAG_score showed that the low TMB+low-risk group had greater OS. Additionally, AAG_score was markedly correlated with chemotherapy and target drug susceptibility.

Conclusion: Our results reveal that AAGs play a significant predictive role in KIRC as a clinical prognostic signature. The relationship between AAGs and TME should provide more potent combination therapy options for patients with KIRC.