Effect of unfolded protein response on the immune infiltration and prognosis of transitional cell bladder cancer

AbstractBackground: Bladder cancer (BC) is one of the most common human malignancies worldwide. Previous researches have shown that the unfolded protein response (UPR) pathway could contribute to the tumorigenesis of BC. However, the role of UPR in the immune infiltration, progression, and prognosis...

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Main Authors: Xiaokai Yan, Min Chen, Chiying Xiao, Jiandong Fu, Xia Sun, Zuohuai Hu, Hang Zhou
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Annals of Medicine
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/07853890.2021.1918346
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author Xiaokai Yan
Min Chen
Chiying Xiao
Jiandong Fu
Xia Sun
Zuohuai Hu
Hang Zhou
author_facet Xiaokai Yan
Min Chen
Chiying Xiao
Jiandong Fu
Xia Sun
Zuohuai Hu
Hang Zhou
author_sort Xiaokai Yan
collection DOAJ
description AbstractBackground: Bladder cancer (BC) is one of the most common human malignancies worldwide. Previous researches have shown that the unfolded protein response (UPR) pathway could contribute to the tumorigenesis of BC. However, the role of UPR in the immune infiltration, progression, and prognosis of BC is unclear.Methods: The GSVA and ssGSEA methods were used for assessing the UPR score and immune cells infiltration score in three BC public datasets, respectively. The relationship between the UPR pathway and clinicopathological characteristics was analyzed by the Kruskal-Wallis, Wilcox test, and log-rank test. The association of the UPR pathway with various tumor-infiltrating immune cells was evaluated with the correlation analysis. Univariate Cox regression analysis was performed to identify risk factors significantly associated with prognosis. The predictive models were built based on risk factors and visualized with nomograms. The performance of our models was evaluated with the calibration curve, Harrell's concordance index (c-index), and receiver operating characteristic (ROC) analysis.Results: We found that the UPR pathway and many UPR-related genes were significantly associated with the pathologic grade, tumor type, and invasive progression of transitional cell bladder cancer (TCBC), and a high UPR score predicted a poor prognosis in patients. The UPR score was positively correlated with the infiltration abundance of many tumor immune cells in TCBC. Besides, we constructed predictive models based on the UPR score, and good performance was observed, with c-indexes ranging from 0.74 to 0.87.Conclusions: Our study proved that the UPR pathway may have an important impact on the progression, prognosis, and tumor immune infiltration in TCBC, and the models we built may provide effective and reliable guides for prognosis assessment and treatment decision-making for TCBC patients.
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spelling doaj.art-2a87791fc3e04170b058df3ad6a4b0c92023-12-19T16:46:27ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602021-01-015311049105910.1080/07853890.2021.1918346Effect of unfolded protein response on the immune infiltration and prognosis of transitional cell bladder cancerXiaokai Yan0Min Chen1Chiying Xiao2Jiandong Fu3Xia Sun4Zuohuai Hu5Hang Zhou6Department of Oncology, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaDepartment of Oncology, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaDepartment of Oncology, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaDepartment of Oncology, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaDepartment of Oncology, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaDepartment of Oncology, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaDepartment of Oncology, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaAbstractBackground: Bladder cancer (BC) is one of the most common human malignancies worldwide. Previous researches have shown that the unfolded protein response (UPR) pathway could contribute to the tumorigenesis of BC. However, the role of UPR in the immune infiltration, progression, and prognosis of BC is unclear.Methods: The GSVA and ssGSEA methods were used for assessing the UPR score and immune cells infiltration score in three BC public datasets, respectively. The relationship between the UPR pathway and clinicopathological characteristics was analyzed by the Kruskal-Wallis, Wilcox test, and log-rank test. The association of the UPR pathway with various tumor-infiltrating immune cells was evaluated with the correlation analysis. Univariate Cox regression analysis was performed to identify risk factors significantly associated with prognosis. The predictive models were built based on risk factors and visualized with nomograms. The performance of our models was evaluated with the calibration curve, Harrell's concordance index (c-index), and receiver operating characteristic (ROC) analysis.Results: We found that the UPR pathway and many UPR-related genes were significantly associated with the pathologic grade, tumor type, and invasive progression of transitional cell bladder cancer (TCBC), and a high UPR score predicted a poor prognosis in patients. The UPR score was positively correlated with the infiltration abundance of many tumor immune cells in TCBC. Besides, we constructed predictive models based on the UPR score, and good performance was observed, with c-indexes ranging from 0.74 to 0.87.Conclusions: Our study proved that the UPR pathway may have an important impact on the progression, prognosis, and tumor immune infiltration in TCBC, and the models we built may provide effective and reliable guides for prognosis assessment and treatment decision-making for TCBC patients.https://www.tandfonline.com/doi/10.1080/07853890.2021.1918346Transitional cell bladder cancerunfolded protein responsetumour immune infiltrationtumour progressionprognostic model
spellingShingle Xiaokai Yan
Min Chen
Chiying Xiao
Jiandong Fu
Xia Sun
Zuohuai Hu
Hang Zhou
Effect of unfolded protein response on the immune infiltration and prognosis of transitional cell bladder cancer
Annals of Medicine
Transitional cell bladder cancer
unfolded protein response
tumour immune infiltration
tumour progression
prognostic model
title Effect of unfolded protein response on the immune infiltration and prognosis of transitional cell bladder cancer
title_full Effect of unfolded protein response on the immune infiltration and prognosis of transitional cell bladder cancer
title_fullStr Effect of unfolded protein response on the immune infiltration and prognosis of transitional cell bladder cancer
title_full_unstemmed Effect of unfolded protein response on the immune infiltration and prognosis of transitional cell bladder cancer
title_short Effect of unfolded protein response on the immune infiltration and prognosis of transitional cell bladder cancer
title_sort effect of unfolded protein response on the immune infiltration and prognosis of transitional cell bladder cancer
topic Transitional cell bladder cancer
unfolded protein response
tumour immune infiltration
tumour progression
prognostic model
url https://www.tandfonline.com/doi/10.1080/07853890.2021.1918346
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