title: PCDH8 is Frequently Inactivated by Promoter Hypermethylation in Liver Cancer: Diagnostic and Clinical Significance.
abstract: OBJECTIVE
  Protocadherin-8 (PCDH8) plays an important role in signaling pathways of cell adhesin, proliferation, and migration. It has been reported that PCDH8 is mutated or methylated in several human cancers. However, little is known about PCDH8 in liver cancer. The aim of this study was to investigate the protein expression and promoter methylation status of PCDH8 in liver cancer and evaluate the association between PCDH8 methylation and the clinicopathological features.
  
  
  METHODS
  The methylation status of PCDH8 in 42 hepatocellular carcinoma (HCC), 8 Cholangiocarcinoma (CC) and 50 normal liver tissues were examined using methylation-specific PCR (MSP) and the protein expression of PCDH8 was detected by immunohistochemistry. The relationships between PCDH8 methylation and clinicopathological features as well as overall survival of patients were evaluated.
  
  
  RESULTS
  The PCDH8 methylation was more frequent in liver cancer tissues than that in the normal liver tissues (88% vs. 32%, P < 0.001), and is significantly associated with loss of its protein expression (P = 0.004). Moreover, there is a significant correlation between PCDH8 methylation and the alpha-fetoprotein (AFP) level (P = 0.008). Kaplan-Meier survival analysis revealed that patients with PCDH8 methylation have shorter OS and PFS than those without PCDH8 methylation (P = 0.041 and P = 0.028, respectively).
  
  
  CONCLUSIONS
  PCDH8 is often inactivated by promoter methylation in liver cancer. PCDH8 methylation can serve as a valuable diagnostic biomarker for early detection of liver cancer and might be useful to predict an unfavorable clinical feature.
authors.affiliation: Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan 250012, P. R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan 250012, P. R. China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan 250012, P. R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan 250012, P. R. China.
authors.forename: Ruixi
authors.initials: R
authors.lastname: Qin
authors.affiliation: Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan 250012, P. R. China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan 250012, P. R. China.
authors.forename: Cuijuan
authors.initials: C
authors.lastname: Zhang
keywords: Liver cancer; PCDH8; Promoter methylation; Protocadherin; Tumor suppressor.