Hypermethylation of protocadherin γ subfamily A12 and solute carrier family 19 A 1 promoters contributes to the occurrence and metastasis of colorectal cancer

Cheng Zhang; Jinyun Li; Tao Huang; Cheng Chen; Qingxiao Hong; Huihui Ji; Meng Ye; Shiwei Duan

doi:10.3892/ol.2018.8393

Hypermethylation of protocadherin γ subfamily A12 and solute carrier family 19 A 1 promoters contributes to the occurrence and metastasis of colorectal cancer

Oncol Lett. 2018 Jun;15(6):8215-8222. doi: 10.3892/ol.2018.8393. Epub 2018 Mar 30.

Authors

Cheng Zhang^{1

2}, Jinyun Li², Tao Huang², Cheng Chen², Qingxiao Hong², Huihui Ji², Meng Ye³, Shiwei Duan²

Affiliations

¹ Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
² Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
³ Department of Medical Oncology, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315020, P.R. China.

Abstract

The development of colorectal cancer (CRC) involves genetic and epigenetic modifications, and aberrant DNA methylation within gene promoters is a primary mediator of epigenetic inheritance in CRC. The present study evaluated whether promoter methylation of four CRC candidate genes [protocadherin γ subfamily A12 (PCDH-γ-A12), solute carrier family 19 A 1 (SLC19A1), cAMP responsive element binding protein (CREB) and cylindromatosis (CYLD) contributed to the risk and metastasis of CRC by screening a total of 42 CRC and 42 adjacent normal tissue samples. DNA methylation was measured by methylation-specific polymerase chain reaction (MSP). Polymerase chain reaction (PCR) products were bisulfite converted and validated by sequencing. The χ² test was employed to assess the association between promoter methylation and a series of clinicopathological characteristics. The promoters of PCDH-γ-A12 and SLC19A1 were observed to be more frequently methylated in CRC tissues than normal tissues. In addition, significantly higher methylation of the PCDH-γ-A12 and SLC19A1 promoters was also observed in CRC tissues with lymph metastasis compared with those without lymph metastasis. In addition, no association was observed between CREB and CYLD methylation and the occurrence and metastasis of CRC. These results suggest that the hypermethylation of the PCDH-γ-A12 and SLC19A1 promoters may contribute to the occurrence and metastasis of CRC in the Han Chinese population.

Keywords: colorectal cancer; metastasis; methylation-specific polymerase chain reaction; promoter; protocadherin γ subfamily A12; solute carrier family 19 A 1.