Methylation-independent CRIP1 expression is a potential biomarker affecting prognosis in cytogenetically normal acute myeloid leukemia.

ABSTRACT

Abnormal expression of CRIP1 has been identified in numerous solid tumors. However, CRIP1 expression and its regulation are little known in acute myeloid leukemia (AML). The purpose of this study was to evaluate the expression and regulation of CRIP1 and the clinical implications of CRIP1 aberration in AML. Real-time quantitative PCR was carried out to detect the level of CRIP1 expression in 138 AML patients and 38 controls. CRIP1 methylation was detected by methylation-specific PCR and bisulfite sequencing PCR. Five public available AML datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were further analyzed. The level of CRIP1 expression was up-regulated in AML patients compared with controls (P = 0.045). CRIP1 high patients had a significantly lower complete remission (CR) rate than CRIP1 low patients (P = 0.020). CRIP1 high group had a shorter overall survival (OS) and leukemia-free survival (LFS) than CRIP1 low group in cytogenetically normal AML (CN-AML) patients (P = 0.007 and 0.012, respectively). Multivariate analysis further confirmed that high CRIP1 expression was an independent risk factor for LFS in CN-AML patients (P = 0.005). However, we found that CRIP1 expression was not associated with the status of its promoter, which was nearly fully unmethylated both in controls and AML patients. Furthermore, our results were validated using the published GEO datasets and TCGA datasets. Our findings suggest that high CRIP1 expression is independently related with unfavorable prognosis in CN-AML.