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

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 progn...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S240584402300868X
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author 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
author_facet 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
author_sort Tianhang Li
collection DOAJ
description 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.
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spelling doaj.art-3cc2ce94ae334049ad4cedf340f544662023-04-05T08:15:47ZengElsevierHeliyon2405-84402023-03-0193e13661Prediction of immune infiltration and prognosis for patients with urothelial bladder cancer based on the DNA damage repair-related genes signatureTianhang Li0Ning Jiang1Yuhao Bai2Tianyao Liu3Zihan Zhao4Xinyan Xu5Yulin Zhang6Fayun Wei7Rui Sun8Siyang Liu9Jiazheng Li10Hongqian Guo11Rong Yang12Department of Urology, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, ChinaNanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, ChinaNanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, ChinaDepartment of Urology, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, ChinaDepartment of Urology, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, ChinaDepartment of Urology, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, ChinaDepartment of Urology, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, ChinaDepartment of Urology, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, ChinaDepartment of Urology, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, ChinaDepartment of Urology, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, ChinaNanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Urology, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China; Corresponding author. 321 Zhongshan Road, Nanjing, Jiangsu 210008, China.Department of Urology, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China; Corresponding author. 321 Zhongshan Road, Nanjing, Jiangsu 210008, China.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.http://www.sciencedirect.com/science/article/pii/S240584402300868XBladder cancerPrognosisDNA Damage repairImmunotherapy
spellingShingle 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
Prediction of immune infiltration and prognosis for patients with urothelial bladder cancer based on the DNA damage repair-related genes signature
Heliyon
Bladder cancer
Prognosis
DNA Damage repair
Immunotherapy
title Prediction of immune infiltration and prognosis for patients with urothelial bladder cancer based on the DNA damage repair-related genes signature
title_full Prediction of immune infiltration and prognosis for patients with urothelial bladder cancer based on the DNA damage repair-related genes signature
title_fullStr Prediction of immune infiltration and prognosis for patients with urothelial bladder cancer based on the DNA damage repair-related genes signature
title_full_unstemmed Prediction of immune infiltration and prognosis for patients with urothelial bladder cancer based on the DNA damage repair-related genes signature
title_short Prediction of immune infiltration and prognosis for patients with urothelial bladder cancer based on the DNA damage repair-related genes signature
title_sort prediction of immune infiltration and prognosis for patients with urothelial bladder cancer based on the dna damage repair related genes signature
topic Bladder cancer
Prognosis
DNA Damage repair
Immunotherapy
url http://www.sciencedirect.com/science/article/pii/S240584402300868X
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