Hypermethylated WNT10A and its clinical significance in colorectal cancer.

Colorectal cancer (CRC) is a heterogeneous disease in which unique subtypes are characterized by distinct genetic and epigenetic alterations. DNA methylation, a well-documented epigenetic modification, is a promising biomarker for the diagnosis and prognosis of cancers, including CRC. WNT10A is a member of the Wnt family. It belongs to the Wnt signaling pathway and is involved in CRC. However, studies regarding the methylation and expression of WNT10A in CRC are limited. In the current study, we analyzed the methylation status of WNT10A in 146 patients with CRC and normal controls. These samples were classified into two groups. The first group was an initial discovery set (i.e., fresh tissue samples from 40 patients with CRC and adjacent normal control samples). The second group was an independent validation set (i.e., formalin-fixed and paraffin-embeded [FFPE] samples from 106 patients with CRC and cutting edge tissues). The results showed a higher level of WNT10A hypermethylation of in CRC samples than in controls (Fresh tissue cohort: P = 2.8E-5; FFPE cohort: P = 3.6E-4).This finding was verified by WNT10A methylation data from The Cancer Genome Atlas portal (TCGA) ( P = 1.9E-83). Subgroup analysis of clinical characteristics showed a higher WNT10A methylation level in elder patients (aged > 60 y) ( P = 0.037) and, patients with distant metastasis ( P = 0.033), rectal cancer ( P = 0.03), and mucinous adenocarcinoma ( P = 0.02). Furthermore, TCGA RNAseq data demonstrated lower WNT10A expression in patients with CRC than in controls ( P = 4.0E-3) and showed a negative correlation between expression and methylation (r = -0.37, P = 5.7E-13). Moreover, the efficiency of WNT10A methylation for CRC diagnosis was analyzed in both cohorts of the present study and the TCGA cohorts, which indicated the potential use of WNT10A methylation as a tool for diagnosis of CRC.