Hypermethylated WNT10A and its clinical significance in colorectal cancer - PubMed (original) (raw)

. 2018 Dec 15;10(12):4290-4301.

eCollection 2018.

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Hypermethylated WNT10A and its clinical significance in colorectal cancer

Haizhong Jiang et al. Am J Transl Res. 2018.

Abstract

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.

Keywords: CRC; DNA methylation; TCGA; WNT10A; diagnosis.

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Conflict of interest statement

None.

Figures

Figure 1

Figure 1

The detail information of the WNT10A gene. Each of the cg loci of WNT10A is labeled in the last layer according to its position; the yellow bar is the amplified segment of WNT10A in the current study; the green bands in the second layer indicate the CpG islands of WNT10A; the information of the layered H3K27Ac and the Txn factor chip are shown in the third and fourth layer. This information was downloaded from the UCSC Genome Browser (http://genome.ucsc.edu/).

Figure 2

Figure 2

Comparison of WNT10A methylation between CRCs and controls in the cohorts of the present study. A: Comparison of WNT10A methylation between 40 paired CRCs and control samples in the fresh tissue cohort. B: Comparison of WNT10A methylation between 106 paired CRCs and control samples in the FFPE cohort.

Figure 3

Figure 3

Diagnostic power of methylated WNT10A in distinguishing of CRC from controls in the cohorts of the present study. A: Diagnostic power of detection of methylated WNT10A in distinguishing of CRC from controls in the fresh tissue cohort. B: Diagnostic power of detection of methylated WNT10A in distinguishing of CRC from controls in the FFPE cohort.

Figure 4

Figure 4

Validation of WNT10A methylation from TCGA dataset. A: Comparison of WNT10A methylation between patients with CRC and controls in TCGA cohorts. B: Diagnostic power of methylated WNT10A in distinguishing of patients with CRC from controls in TCGA cohorts. C: Comparison of WNT10A expression between patients with CRC and controls from TCGA portal. D: Negative correlation of WNT10A methylation and expression from TCGA portal.

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