Comprehensive DNA repair gene expression analysis and its prognostic significance in acute myeloid leukemia

Sholhui Park, Yi Jun Kim, Hee Jin Huh, Hae Sun Chung, Miae Lee, Young Mi Park, Yeung Chul Mun, Chu Myong Seong, Jungwon Huh

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Deficiency in DNA damage response (DDR) pathway and accumulation of DNA damage increases mutation rates resulting in genomic instability and eventually increases the risk of cancer. The aim of our study was to investigate expressions of DNA repair genes as new prognostic biomarkers in acute myeloid leukemia (AML). Methods: We utilized The Cancer Genome Atlas AML project (TCGA-LAML cohort, 15 acute promyelocytic leukemia (APL) and 155 non-APL AML) for the expression data of DNA repair genes. For validation, clinical samples (Ewha study group, 9 APL and 72 non-APL AML patients) were analyzed for the expression of 22 DNA repair genes using a custom RT2 Profiler PCR Array. Results: APL patients presented significantly lower expression of DNA repair genes than non-APL AML patients in both study groups. Among non-APL AML patients, high expression levels of PARP1, XRCC1, and RAD51 were associated with poor overall survival (OS) probability in both study groups. Furthermore, Cox regression analysis showed that increased expression levels of PARP1, XRCC1, RAD51, BRCA1 and MRE11A could be independent risk factors for OS in the Ewha study group. Among non-APL patients of the Ewha study group, the OS probability of DDR-overexpressed group with at least one gene or more showing Z score greater than 1.5 was poorer than that of DDR non-overexpressed group. Conclusion: In the current study, the DNA repair gene expression profile of APL patients was different from that of non-APL AML patients. Overexpression of DNA repair genes could be a poor prognostic biomarker in non-APL AML.

Original languageEnglish
Pages (from-to)904-913
Number of pages10
JournalHematology
Volume26
Issue number1
DOIs
StatePublished - 2021

Keywords

  • DNA damage response
  • DNA repair gene
  • PARP inhibitors
  • TCGA
  • acute myeloid leukemia
  • biomarker
  • gene expression profile
  • prognosis

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