Hypermethylation of miR-34b/c is associated with early clinical stages and tumor differentiation in Kazakh patients with esophageal squamous cell carcinoma

DNA hypermethylation in tumor suppressor genes has been reported in some cancers. The microRNA-34b/c (miR-34b/c) serves as tumor suppressors in different tumor types. To investigate the methylation status of miR-34b/c in ESCC, MALDI-TOF MS was used to quantitatively analyze the DNA methylation of 16 CpG sites within miR-34b/c in 145 ESCC samples, 60 cancer-adjacent normal (ACN) samples and 39 normal esophageal (NE) samples from the Kazakh population. Our results showed that the overall average methylation levels of miR-34b/c were significantly higher in the ESCC samples than they were in the ACN and NE samples (P < 0.05). Furthermore, the methylation levels of CpG_1.2.3, CpG_9.10, CpG_11.12.13, CpG_14, and CpG_15.16 of miR-34b/c were significantly higher in the ESCC tissues than they were in the ACN (P < 0.05) and NE tissues (P < 0.05). Additionally, the mean methylation levels at CpG_9.10 and CpG_14 were all significantly higher in the ACN samples than they were in the NE samples (P < 0.01). Increased methylation levels of CpG_9.10 and CpG_11.12.13 in miR-34b/c predominantly occurred in the early stages (UICC I/II) of ESCC (P < 0.05), and the methylation differences (moderately-poorly differentiated > well differentiated) in miR-34b/c CpG_1.2.3 were significant (P < 0.05). This is the first study reporting that the hypermethylation of miR-34b/c plays an important role in ESCC and is significantly correlated with the early stages and tumor differentiation of ESCC. The hypermethylation of miR-34b/c may promote the oncogenesis and progression of ESCC, and these findings may provide support for the future development of targeted therapies.