Identification of DNA Damage Repair-Associated Prognostic Biomarkers for Prostate Cancer Using Transcriptomic Data Analysis

In the recent decade, the importance of DNA damage repair (DDR) and its clinical application have been firmly recognized in prostate cancer (PC). For example, olaparib was just approved in May 2020 to treat metastatic castration-resistant PC with homologous recombination repair-mutated genes; howeve...

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Autores principales:	Pai-Chi Teng, Shu-Pin Huang, Chia-Hsin Liu, Ting-Yi Lin, Yi-Chun Cho, Yo-Liang Lai, Shu-Chi Wang, Hsin-Chih Yeh, Chih-Pin Chuu, Deng-Neng Chen, Wei-Chung Cheng, Chia-Yang Li
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	prostate cancer (PC) DNA damage repair (DDR) DDR-based transcriptomic biomarker prognostic marker cancer survival Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/86ef3631092c42d48c72b27ec1f85b11
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spelling	oai:doaj.org-article:86ef3631092c42d48c72b27ec1f85b112021-11-11T17:13:27ZIdentification of DNA Damage Repair-Associated Prognostic Biomarkers for Prostate Cancer Using Transcriptomic Data Analysis10.3390/ijms2221117711422-00671661-6596https://doaj.org/article/86ef3631092c42d48c72b27ec1f85b112021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11771https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067In the recent decade, the importance of DNA damage repair (DDR) and its clinical application have been firmly recognized in prostate cancer (PC). For example, olaparib was just approved in May 2020 to treat metastatic castration-resistant PC with homologous recombination repair-mutated genes; however, not all patients can benefit from olaparib, and the treatment response depends on patient-specific mutations. This highlights the need to understand the detailed DDR biology further and develop DDR-based biomarkers. In this study, we establish a four-gene panel of which the expression is significantly associated with overall survival (OS) and progression-free survival (PFS) in PC patients from the TCGA-PRAD database. This panel includes <i>DNTT</i>, <i>EXO1</i>, <i>NEIL3</i>, and <i>EME2</i> genes. Patients with higher expression of the four identified genes have significantly worse OS and PFS. This significance also exists in a multivariate Cox regression model adjusting for age, PSA, TNM stages, and Gleason scores. Moreover, the expression of the four-gene panel is highly correlated with aggressiveness based on well-known PAM50 and PCS subtyping classifiers. Using publicly available databases, we successfully validate the four-gene panel as having the potential to serve as a prognostic and predictive biomarker for PC specifically based on DDR biology.Pai-Chi TengShu-Pin HuangChia-Hsin LiuTing-Yi LinYi-Chun ChoYo-Liang LaiShu-Chi WangHsin-Chih YehChih-Pin ChuuDeng-Neng ChenWei-Chung ChengChia-Yang LiMDPI AGarticleprostate cancer (PC)DNA damage repair (DDR)DDR-based transcriptomic biomarkerprognostic markercancer survivalBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11771, p 11771 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	prostate cancer (PC) DNA damage repair (DDR) DDR-based transcriptomic biomarker prognostic marker cancer survival Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	prostate cancer (PC) DNA damage repair (DDR) DDR-based transcriptomic biomarker prognostic marker cancer survival Biology (General) QH301-705.5 Chemistry QD1-999 Pai-Chi Teng Shu-Pin Huang Chia-Hsin Liu Ting-Yi Lin Yi-Chun Cho Yo-Liang Lai Shu-Chi Wang Hsin-Chih Yeh Chih-Pin Chuu Deng-Neng Chen Wei-Chung Cheng Chia-Yang Li Identification of DNA Damage Repair-Associated Prognostic Biomarkers for Prostate Cancer Using Transcriptomic Data Analysis
description	In the recent decade, the importance of DNA damage repair (DDR) and its clinical application have been firmly recognized in prostate cancer (PC). For example, olaparib was just approved in May 2020 to treat metastatic castration-resistant PC with homologous recombination repair-mutated genes; however, not all patients can benefit from olaparib, and the treatment response depends on patient-specific mutations. This highlights the need to understand the detailed DDR biology further and develop DDR-based biomarkers. In this study, we establish a four-gene panel of which the expression is significantly associated with overall survival (OS) and progression-free survival (PFS) in PC patients from the TCGA-PRAD database. This panel includes <i>DNTT</i>, <i>EXO1</i>, <i>NEIL3</i>, and <i>EME2</i> genes. Patients with higher expression of the four identified genes have significantly worse OS and PFS. This significance also exists in a multivariate Cox regression model adjusting for age, PSA, TNM stages, and Gleason scores. Moreover, the expression of the four-gene panel is highly correlated with aggressiveness based on well-known PAM50 and PCS subtyping classifiers. Using publicly available databases, we successfully validate the four-gene panel as having the potential to serve as a prognostic and predictive biomarker for PC specifically based on DDR biology.
format	article
author	Pai-Chi Teng Shu-Pin Huang Chia-Hsin Liu Ting-Yi Lin Yi-Chun Cho Yo-Liang Lai Shu-Chi Wang Hsin-Chih Yeh Chih-Pin Chuu Deng-Neng Chen Wei-Chung Cheng Chia-Yang Li
author_facet	Pai-Chi Teng Shu-Pin Huang Chia-Hsin Liu Ting-Yi Lin Yi-Chun Cho Yo-Liang Lai Shu-Chi Wang Hsin-Chih Yeh Chih-Pin Chuu Deng-Neng Chen Wei-Chung Cheng Chia-Yang Li
author_sort	Pai-Chi Teng
title	Identification of DNA Damage Repair-Associated Prognostic Biomarkers for Prostate Cancer Using Transcriptomic Data Analysis
title_short	Identification of DNA Damage Repair-Associated Prognostic Biomarkers for Prostate Cancer Using Transcriptomic Data Analysis
title_full	Identification of DNA Damage Repair-Associated Prognostic Biomarkers for Prostate Cancer Using Transcriptomic Data Analysis
title_fullStr	Identification of DNA Damage Repair-Associated Prognostic Biomarkers for Prostate Cancer Using Transcriptomic Data Analysis
title_full_unstemmed	Identification of DNA Damage Repair-Associated Prognostic Biomarkers for Prostate Cancer Using Transcriptomic Data Analysis
title_sort	identification of dna damage repair-associated prognostic biomarkers for prostate cancer using transcriptomic data analysis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/86ef3631092c42d48c72b27ec1f85b11
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Identification of DNA Damage Repair-Associated Prognostic Biomarkers for Prostate Cancer Using Transcriptomic Data Analysis

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