PCDHB15 as a potential tumor suppressor and epigenetic biomarker for breast cancer

Abstract

Breast cancer is among the most frequently diagnosed cancer types and the leading cause of cancer-related death in women. The mortality rate of patients with breast cancer is currently increasing, perhaps due to a lack of early screening tools. In the present study, using The Cancer Genome Atlas (TCGA) breast cancer dataset (n=883), it was determined that methylation of the protocadherin β15 (PCDHB15) promoter was higher in breast cancer samples than that in normal tissues. A negative association between promoter methylation and expression of PCDHB15 was observed in the TCGA dataset and breast cancer cell lines. In TCGA cohort, lower PCDHB15 expression was associated with shorter relapse-free survival times. Treatment with the DNA methyltransferase inhibitor restored PCDHB15 expression in a breast cancer cell line; however, overexpression of PCDHB15 was shown to suppress colony formation. PCDHB15 methylation detected in circulating cell-free DNA (cfDNA) isolated from serum samples was higher in patients with breast cancer (40.8%) compared with that in patients with benign tumors (22.4%). PCDHB15 methylation was not correlated with any clinical parameters. Taken together, PCDHB15 is a potential tumor suppressor in cases of breast cancer, which can be epigenetically silenced via promoter methylation. PCDHB15 methylation using cfDNA is a novel minimally invasive epigenetic biomarker for the diagnosis and prognosis of breast cancer.

Differential methylation pattern in pubertal girls associated with biochemical premature adrenarche

“…The CpG site cg13337064, for which methylation status at Tanner 2 correlated with HOMA-IR and insulin level at Tanner 1 ( Figure 3 A ), is in exon 1 of gene PCDHB15 (Gene ID: 56121). It has recently been shown that PCDHB15 can be epigenetically silenced via promoter methylation [ 43 ].…”

Elucidating Novel Targets for Ovarian Cancer Antibody–Drug Conjugate Development: Integrating In Silico Prediction and Surface Plasmon Resonance to Identify Targets with Enhanced Antibody Internalization Capacity

“…PCDHB10 and PCDHB15 are members of the cadherin superfamily of calcium-dependent cell–cell adhesion molecules; PCDHB10 is involved in the establishment and maintenance of neuronal functions in the brain and is implicated in paediatric malignancies [ 40 ]. PCDHB15 is involved in cell adhesion, and it is epigenetically regulated in melanoma and breast cancer cells [ 41 , 42 ]. Furthermore, OPRK1 has been implicated in facilitating the migration of breast cancer cells, while the low expression of GABRB1 correlated with a poor prognosis in colon adenocarcinoma [ 43 , 44 ].…”

Epigenetically regulated PCDHB15 impairs aggressiveness of metastatic melanoma cells

“…Of note, the demethylation by 5azadC reached a plateau at 55%, probably meaning that all the accessible cytosines in the DNA sequence were replaced by 5azadC. Interestingly, a negative correlation between PCDHB15 promoter methylation and PCDHB15 expression was also reported in breast cancer [ 49 ]. Nevertheless, whereas these data strongly pointed out the role of DNA methylation in the regulation of PCDHB15 expression, the direct involvement of the methylation in the regulatory regions at the 5′ end of the gene remains to be confirmed.…”

“…A functional role for the hypermethylation and gene silencing of PCDHαβγ family genes ( PCDHAC2 , PCDHB7 , PCDHB15 , PCDHGA1 and PCDHGA6 ) was also identified recently in colorectal cancer influencing the WNT/B-catenin pathway implicated in proliferation, survival and migration [ 56 ]. More recently, PCDHB15 was proposed as a potential tumor suppressor in breast cancer, based on the observation of a positive correlation between PCDHB15 expression and relapse-free survival [ 49 ]. Interestingly, ectopic expression of PCDHB15 , which is down-regulated by DNA methylation in the MDA-MB-231 breast cell line, suppressed colony formation.…”