Identification and validation of SRY-box containing gene family member methylation as a prognostic and predictive biomarker in myeloid malignancies.

Background: Methylation-associated family genes have been proved to be involved in multiple essential processes during carcinogenesis and act as potential biomarkers for cancer diagnosis, staging, prediction of prognosis, and monitoring of response to therapy. Herein, we revealed methylation and its clinical implication in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

Results: In the discovery stage, we identified that methylation, a frequent event in AML, was negatively associated with expression and correlated with overall survival (OS) and leukemia-free survival (LFS) in cytogenetically normal AML among family members from The Cancer Genome Atlas (TCGA) datasets. In the validation stage, we verified that methylation level was significantly higher in AML even in MDS-derived AML compared to controls, whereas hypermethylation was not a frequent event in MDS. methylation was inversely correlated with expression in AML patients. Survival analysis showed that hypermethylation was negatively associated with complete remission (CR), OS, and LFS in AML, where it only affected LFS in MDS. Notably, among MDS/AML paired patients, methylation level was significantly increased in AML stage than in MDS stage. In addition, methylation was found to be significantly decreased in AML achieved CR when compared to diagnosis time and markedly increased in relapsed AML when compared to the CR population.

Conclusions: Our findings revealed that methylation was associated with disease progression in MDS and acted as an independent prognostic and predictive biomarker in AML.