Prediction of immune infiltration and prognosis for patients with urothelial bladder cancer based on the DNA damage repair-related genes signature

Tianhang Li; Ning Jiang; Yuhao Bai; Tianyao Liu; Zihan Zhao; Xinyan Xu; Yulin Zhang; Fayun Wei; Rui Sun; Siyang Liu; Jiazheng Li; Hongqian Guo; Rong Yang

doi:10.1016/j.heliyon.2023.e13661

Prediction of immune infiltration and prognosis for patients with urothelial bladder cancer based on the DNA damage repair-related genes signature

Heliyon. 2023 Feb 13;9(3):e13661. doi: 10.1016/j.heliyon.2023.e13661. eCollection 2023 Mar.

Authors

Tianhang Li¹, Ning Jiang², Yuhao Bai², Tianyao Liu¹, Zihan Zhao¹, Xinyan Xu¹, Yulin Zhang¹, Fayun Wei¹, Rui Sun¹, Siyang Liu¹, Jiazheng Li³, Hongqian Guo¹, Rong Yang¹

Affiliations

¹ Department of Urology, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China.
² Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China.
³ Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.

Abstract

Objectives: To analyze the correlations between the expression and effect of DNA damage repair genes and the immune status and clinical outcomes of urothelial bladder cancer (BLCA) patients. In addition, we evaluate the efficacy and value of utilizing the DNA damage repair genes signature as a prognosis model for BLCA.

Methods: Two subtype groups (C1 and C2) were produced based on the varied expression of DNA damage repair genes. Significantly differentiated genes and predicted enriched gene pathways were obtained between the two subtypes. Seven key genes were obtained from the DNA damage repair-related genes and a 7-gene signature prognosis model was established based on the key genes. The efficacy and accuracy of this model in prognosis prediction was evaluated and verified in two independent databases. Also, the difference in biological functions, drug sensitivity, immune infiltration and affinity between the high-risk group and low-risk group was analyzed.

Results: The DNA damage repair gene signature could significantly differentiate the BLCA into two molecular subgroups with varied genetic expression and enriched gene pathways. Seven key genes were screened out from the 232 candidate genes for prognosis prediction and a 7-gene signature prognosis model was established based on them. Two independent patient cohorts (TCGA cohort and GEO cohort) were utilized to validate the efficacy of the prognosis model, which demonstrated an effective capability to differentiate and predict the overall survival of BLCA patients. Also, the high-risk group and low-risk group derived from the 7-gene model exhibited significantly differences in drug sensitivity, immune infiltration status and biological pathways enrichment.

Conclusions: Our established 7-gene signature model based on the DNA damage repair genes could serve as a novel prognosis predictive tool for BLCA. The differentiation of BLCA patients based on the 7-gene signature model may be of great value for the appropriate selection of specific chemotherapy agents and immune-checkpoint blockade therapy administration.

Keywords: Bladder cancer; DNA Damage repair; Immunotherapy; Prognosis.