In:
Cancer Science, Wiley, Vol. 106, No. 9 ( 2015-09), p. 1153-1162
Abstract:
It has become evident that P‐cadherin, one of the classical cadherins, contributes to the malignant behavior of several types of cancer. In this study, we analyzed the expression of P‐cadherin and its clinicopathological and prognostic values in intrahepatic cholangiocarcinoma ( ICC ) and pancreatic cancer. Furthermore, we investigated the functional role of P‐cadherin in these cancer cells by knockdown and overexpression in vitro and by analyzing the correlation between the P‐cadherin expression and its promoter methylation status. Thirty of 59 ICC cases (51%) and 36 of 73 pancreatic cancer cases (49%) stained positive for P‐cadherin with mainly membranous distribution in tumor cells by immunohistochemistry. P‐cadherin expression was significantly correlated with several clinicopathological factors, which reflect tumor behavior, and was identified as an independent adverse prognostic factor for disease‐free survival in patients with ICC (relative risk [ RR ] 2.93, P = 0.04) and pancreatic cancer ( RR 2.68, P = 0.005) via multivariate analyses. P‐cadherin downregulation by si RNA suppressed migration and invasion, and P‐cadherin overexpression induced the opposite effects in both ICC and pancreatic cancer cells, without any effects on cell proliferation. P‐cadherin expression was related to its promoter methylation status in both cell lines and cancer tissues. In summary, P‐cadherin overexpression may serve as a useful biomarker of invasive phenotype and poor prognosis; P‐cadherin expression was found to be regulated by its promoter methylation. These results suggest that P‐cadherin represents a novel therapeutic target for the treatment of ICC and pancreatic cancer.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2015.106.issue-9
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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