Comprehensive DNA repair gene expression analysis and its prognostic significance in acute myeloid leukemia
- 주제(키워드) DNA repair gene , gene expression profile , acute myeloid leukemia , prognosis , biomarker , DNA damage response , PARP inhibitors , TCGA
- 주제(기타) Hematology
- 설명문(일반) [Park, Sholhui; Chung, Hae-Sun; Lee, Miae; Huh, Jungwon] Ewha Womans Univ, Coll Med, Dept Lab Med, Seoul, South Korea; [Kim, Yi-Jun] Ewha Womans Univ, Inst Convergence Med, Mokdong Hosp, Seoul, South Korea; [Huh, Hee Jin] Dongguk Univ, Dept Lab Med, Ilsan Hosp, Goyang, South Korea; [Park, Young Mi] Ewha Womans Univ, Coll Med, Dept Mol Med, Seoul, South Korea; [Mun, Yeung Chul; Seong, Chu-Myong] Ewha Womans Univ, Coll Med, Dept Internal Med, Seoul, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold
- 발행기관 TAYLOR & FRANCIS LTD
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000183843
- 본문언어 영어
- Published As http://dx.doi.org/10.1080/16078454.2021.1997196
- PubMed https://pubmed.ncbi.nlm.nih.gov/34789078
초록/요약
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.
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