PCDHB15 as a potential tumor suppressor and epigenetic biomarker for breast cancer
Ching‐Chung Chiang, Guan‐Ling Lin, Shuyi Yang, Chi‐Wen Tu, Wenlong Huang, Chun-Feng Wei, Fengchi Wang, Pin-Ju Lin, Wan-Hong Huang, Yu‐Ming Chuang, Yu‐Ting Lee, Chia-Chou Yeh, Michael W.Y. Chan, Yu-chen Hsu
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 (<em>PCDHB15</em>) promoter was higher in breast cancer samples than that in normal tissues. A negative association between promoter methylation and expression of <em>PCDHB15</em> was observed in the TCGA dataset and breast cancer cell lines. In TCGA cohort, lower <em>PCDHB15</em> expression was associated with shorter relapse‑free survival times. Treatment with the DNA methyltransferase inhibitor restored <em>PCDHB15</em> expression in a breast cancer cell line; however, overexpression of <em>PCDHB15</em> was shown to suppress colony formation. <em>PCDHB15</em> 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%). <em>PCDHB15</em> methylation was not correlated with any clinical parameters. Taken together, <em>PCDHB15</em> is a potential tumor suppressor in cases of breast cancer, which can be epigenetically silenced via promoter methylation. <em>PCDHB15</em> methylation using cfDNA is a novel minimally invasive epigenetic biomarker for the diagnosis and prognosis of breast cancer.