The prognostic potential and oncogenic effects of PRR11 expression in hilar cholangiocarcinoma

2015 
// Ying Chen 1,* , Zhanshan Cha 2,* , Wenzheng Fang 3,* , Baohua Qian 2 , Wenlong Yu 4 , Wenfeng Li 5 , Guanzhen Yu 6,7 and Yong Gao 7 1 Department of Pathology, Changhai Hospital, Shanghai, China 2 Department of Transfusion, Changhai Hospital, Shanghai, China 3 Department of Oncology, Fuzhou General Hospital, Fuzhou, Fujian Province, China 4 Department of Surgery, Eastern Hepatobiliary Hospital, Shanghai, China 5 Department of Radiation Oncology, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China 6 Department of Medical Oncology, Changzheng Hospital, Shanghai, China 7 Department of Oncology, East Hospital, Tongji University School of Medicine, Shanghai, China * These authors have contributed equally to this work Correspondence to: Guanzhen Yu, email: // Wenfeng Li, email: // Keywords : PRR11; hilar cholangiocarcinoma; oncogene; prognosis Received : December 29, 2014 Accepted : April 10, 2015 Published : May 04, 2015 Abstract PRR11 is a newly identified oncogene in lung cancer, yet its role in others tumors remains unclear. Gastrointestinal tissue microarrays were used to evaluate PRR11 expression and its association with clinical outcome was analyzed in patients with hilar cholangiocarcinoma. Overexpression of PRR11 was observed in esophageal, gastric, pancreatic, colorectal, and hilar cholangiocarcinoma. Expression of PRR11 correlated with lymph node metastasis and CA199 level in two HC patient cohorts. After an R0 resection, a high level of PRR11 expression was found to be an independent indicator of recurrence ( P = 0.001). In cell culture, PRR11 silencing resulted in decreased cellular proliferation, cell migration, tumor growth of QBC939 cells. Microarray analysis revealed that several genes involved in cell proliferation, cell adhesion, and cell migration were altered in PRR11-knockout cells, including: vimentin (VIM), Ubiquitin carboxyl-terminal hydrolase 1 (UCHL1), early growth response protein (EGR1), and System A amino acid transporter1 (SNAT1). Silencing PRR11 inhibited the expression of UCHL1, EGR1, and SNAT1 proteins, with immunoassays revealing a significant correlation among the levels of these four proteins. These results indicate that PRR11 is an independent prognostic indicator for patients with HC.
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