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

Title
Comprehensive DNA repair gene expression analysis and its prognostic significance in acute myeloid leukemia
Authors
Park, SholhuiKim, Yi-JunHuh, Hee JinChung, Hae-SunLee, MiaePark, Young MiMun, Yeung ChulSeong, Chu-MyongHuh, Jungwon
Ewha Authors
이미애성주명허정원문영철박영미정혜선박설희김이준
SCOPUS Author ID
이미애scopus; 성주명scopus; 허정원scopus; 문영철scopus; 박영미scopus; 정혜선scopus; 박설희scopus; 김이준scopus
Issue Date
2021
Journal Title
HEMATOLOGY
ISSN
1024-5332JCR Link

1607-8454JCR Link
Citation
HEMATOLOGY vol. 26, no. 1, pp. 904 - 913
Keywords
DNA repair genegene expression profileacute myeloid leukemiaprognosisbiomarkerDNA damage responsePARP inhibitorsTCGA
Publisher
TAYLOR &

FRANCIS LTD
Indexed
SCIE; SCOPUS WOS
Document Type
Article
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.
DOI
10.1080/16078454.2021.1997196
Appears in Collections:
의과대학 > 의학과 > Journal papers
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