Identification of dna damage repair-associated prognostic biomarkers for prostate cancer using transcriptomic data analysis

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

Research output: Contribution to journalArticlepeer-review

Abstract

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-mu-tated genes; however, not all patients can benefit from olaparib, and the treatment response de-pends 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 DNTT, EXO1, NEIL3, and EME2 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 ad-justing 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 hav-ing the potential to serve as a prognostic and predictive biomarker for PC specifically based on DDR biology.

Original languageEnglish (US)
Article number11771
JournalInternational journal of molecular sciences
Volume22
Issue number21
DOIs
StatePublished - Nov 1 2021
Externally publishedYes

Keywords

  • Cancer survival
  • DDR-based transcriptomic biomarker
  • DNA damage repair (DDR)
  • Prognostic marker
  • Prostate cancer (PC)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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