Decreased 5-Hydroxymethylcytosine (5-hmC) predicts poor prognosis in early-stage laryngeal squamous cell carcinoma

Accumulating evidences suggest that large-scale loss of 5-hydroxymethylcytosine (5-hmC) is an epigenetic hallmark in different cancers. However, the levels of 5-hmC in laryngeal squamous cell carcinoma (LSCC) and its prognostic value in this cancer remain largely unknown. Using dot-blot and quantitative RT-PCR assays, we investigate 5-hmC levels and expression of TET-1, -2 and -3 in LSCCs and explore the association of 5-hmC levels with clinicopathological characteristics and clinical outcome of LSCC patients. Our data showed that 5-hmC was significantly decreased in LSCCs as compared with matched normal tissues. We also found a strong link between decreased 5-hmC and the reduction of TET-1 gene expression, but not TET-2 or -3, suggesting that decreased TET-1 expression was implicated in 5-hmC loss in LSCC. Moreover, Mann-Whitney U tests showed that 5-hmC content was significantly associated with smoking (P = 0.039) and tumor invasion (P = 0.004). Importantly, we found that decreased 5-hmC was significantly associated with poor survival of early-stage LSCC patients (P = 0.043). Altogether, our findings implicate that decreased 5-hmC probaly caused by the reduction of TET-1 is crucial to the clinical pathology of LSCC and is a poor prognostic factor in ealry-stage LSCC patients.