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Immune infiltration phenotypes of prostate adenocarcinoma and their clinical implications

BACKGROUND: Tumor‐infiltrating immune cells participate in the initiation and progression of prostate adenocarcinoma (PRAD). However, it is not fully known how immune infiltration affects the development of PRAD and its clinical presentation. METHODS: Herein, we investigated the immune infiltration...

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Autores principales: Ma, Zehua, Cheng, Xiankui, Yue, Ting, Shangguan, Xun, Xin, Zhixiang, Zhang, Weiwei, Pan, Jiahua, Wang, Qi, Xue, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335836/
https://www.ncbi.nlm.nih.gov/pubmed/34128342
http://dx.doi.org/10.1002/cam4.4063
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author Ma, Zehua
Cheng, Xiankui
Yue, Ting
Shangguan, Xun
Xin, Zhixiang
Zhang, Weiwei
Pan, Jiahua
Wang, Qi
Xue, Wei
author_facet Ma, Zehua
Cheng, Xiankui
Yue, Ting
Shangguan, Xun
Xin, Zhixiang
Zhang, Weiwei
Pan, Jiahua
Wang, Qi
Xue, Wei
author_sort Ma, Zehua
collection PubMed
description BACKGROUND: Tumor‐infiltrating immune cells participate in the initiation and progression of prostate adenocarcinoma (PRAD). However, it is not fully known how immune infiltration affects the development of PRAD and its clinical presentation. METHODS: Herein, we investigated the immune infiltration phenotypes in PRAD based on transcriptome profiles, methylation profiles, somatic mutation, and copy number variations. We also developed an immune prognostic model (IPM) to identify unfavorable prognosis. To verify this model, immunohistochemistry staining was performed on a cohort of PRAD samples. Moreover, we constructed a nomogram to assess the survival of PRAD incorporating immune infiltration and other clinical features. RESULTS: We categorized PRAD patients into high and low‐level clusters based on immune infiltration phenotypes. The patients in the high‐level clusters had worse survival than their low‐level counterparts. Gene set enrichment analysis indicated that both anti‐ and pro‐tumor terms were enriched in high‐level cluster. Moreover, we identified a positive correlation between anti‐ and pro‐tumor immune cells in PRAD microenvironment. Notably, Somatic mutation analysis showed patients in high‐level cluster had a higher somatic mutation burden of KMT2D, HSPA8, CHD7, and MAP1A. In addition, we developed an IPM with robust predictive ability. The model can distinguish high‐risk PRAD patients with poor prognosis from low‐risk PRAD patients in both training and another three independent validation datasets. Besides, we constructed a nomogram incorporating Gleason score, pathological T stage, and IPM for the prognosis prediction of PRAD patients, which displayed robust predictive ability and might contribute to clinical practice. CONCLUSION: Our work illustrated the immune infiltration phenotypes strongly related to the poor prognosis of PRAD patients, and highlighted the potential of the IPM to identify unfavorable tumor features.
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spelling pubmed-83358362021-08-09 Immune infiltration phenotypes of prostate adenocarcinoma and their clinical implications Ma, Zehua Cheng, Xiankui Yue, Ting Shangguan, Xun Xin, Zhixiang Zhang, Weiwei Pan, Jiahua Wang, Qi Xue, Wei Cancer Med Bioinformatics BACKGROUND: Tumor‐infiltrating immune cells participate in the initiation and progression of prostate adenocarcinoma (PRAD). However, it is not fully known how immune infiltration affects the development of PRAD and its clinical presentation. METHODS: Herein, we investigated the immune infiltration phenotypes in PRAD based on transcriptome profiles, methylation profiles, somatic mutation, and copy number variations. We also developed an immune prognostic model (IPM) to identify unfavorable prognosis. To verify this model, immunohistochemistry staining was performed on a cohort of PRAD samples. Moreover, we constructed a nomogram to assess the survival of PRAD incorporating immune infiltration and other clinical features. RESULTS: We categorized PRAD patients into high and low‐level clusters based on immune infiltration phenotypes. The patients in the high‐level clusters had worse survival than their low‐level counterparts. Gene set enrichment analysis indicated that both anti‐ and pro‐tumor terms were enriched in high‐level cluster. Moreover, we identified a positive correlation between anti‐ and pro‐tumor immune cells in PRAD microenvironment. Notably, Somatic mutation analysis showed patients in high‐level cluster had a higher somatic mutation burden of KMT2D, HSPA8, CHD7, and MAP1A. In addition, we developed an IPM with robust predictive ability. The model can distinguish high‐risk PRAD patients with poor prognosis from low‐risk PRAD patients in both training and another three independent validation datasets. Besides, we constructed a nomogram incorporating Gleason score, pathological T stage, and IPM for the prognosis prediction of PRAD patients, which displayed robust predictive ability and might contribute to clinical practice. CONCLUSION: Our work illustrated the immune infiltration phenotypes strongly related to the poor prognosis of PRAD patients, and highlighted the potential of the IPM to identify unfavorable tumor features. John Wiley and Sons Inc. 2021-06-15 /pmc/articles/PMC8335836/ /pubmed/34128342 http://dx.doi.org/10.1002/cam4.4063 Text en © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Bioinformatics
Ma, Zehua
Cheng, Xiankui
Yue, Ting
Shangguan, Xun
Xin, Zhixiang
Zhang, Weiwei
Pan, Jiahua
Wang, Qi
Xue, Wei
Immune infiltration phenotypes of prostate adenocarcinoma and their clinical implications
title Immune infiltration phenotypes of prostate adenocarcinoma and their clinical implications
title_full Immune infiltration phenotypes of prostate adenocarcinoma and their clinical implications
title_fullStr Immune infiltration phenotypes of prostate adenocarcinoma and their clinical implications
title_full_unstemmed Immune infiltration phenotypes of prostate adenocarcinoma and their clinical implications
title_short Immune infiltration phenotypes of prostate adenocarcinoma and their clinical implications
title_sort immune infiltration phenotypes of prostate adenocarcinoma and their clinical implications
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335836/
https://www.ncbi.nlm.nih.gov/pubmed/34128342
http://dx.doi.org/10.1002/cam4.4063
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