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

• Published in: Hematology (Luxembourg) 2021-01, Vol.26 (1), p.904-913
• Main Authors: Park, Sholhui, Kim, Yi-Jun, Huh, Hee Jin, Chung, Hae-Sun, Lee, Miae, Park, Young Mi, Mun, Yeung Chul, Seong, Chu-Myong, Huh, Jungwon
• Format: Article
• Language: English
• Subjects: acute myeloid leukemia; Adolescent; Adult; Aged; Aged, 80 and over; biomarker; Biomarkers, Tumor; Combined Modality Therapy; Cytogenetic Analysis; Disease Management; Disease Susceptibility; DNA damage response; DNA Repair; DNA repair gene; Female; gene expression profile; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Humans; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - therapy; Male; Middle Aged; PARP inhibitors; Prognosis; Survival Analysis; TCGA; Transcriptome; Treatment Outcome; Young Adult
• ISSN: 1607-8454; 1607-8454
• DOI: 10.1080/16078454.2021.1997196

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). 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 RT 2 Profiler PCR Array. 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. 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.