Thyroid cancer 1 (C8orf4) shows high expression, no mutation and reduced methylation level in lung cancers, and its expression correlates with β-catenin and DNMT1 expression and poor prognosis
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Yi-Wen Zheng1,*, Li Zhang1,*, Yuan Wang1, Song-Yan Chen1, Lei Lei1, Na Tang1, Da-Lei Yang1, Lin-Lin Bai1, Xiu-Peng Zhang1, Gui-Yang Jiang1, Lian-He Yang1, Hong-Tao Xu1, Qing-Chang Li1, Xue-Shan Qiu1 and En-Hua Wang1
1Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang 110001, China
*These authors have contributed equally to this work
Hong-Tao Xu, email: [email protected]
Keywords: C8orf4, mutation, methylation, β-catenin, DNMT1
Received: February 02, 2017 Accepted: March 21, 2017 Published: April 06, 2017
Thyroid cancer 1 (TC1, C8orf4) plays important roles in tumors. The aim of this study was to examine the protein expression levels, methylation status, and mutational status of TC1 (C8orf4) in lung cancers, and investigate the correlation between TC1, other members of the Wnt signaling pathway, and lung cancer. TC1 expression levels were assessed via immunohistochemical staining in 179 cases of lung cancer. β-catenin, TCF4, Axin, Disabled-2, Chibby, and DNA methyltransferase-1 (DNMT1) expressions were also examined. Bisulfite sequencing PCR analysis was used to examine the methylation status of the C8orf4 locus, while PCR analysis and direct sequencing were used to determine its mutational status. We found high TC1 expression correlated with poor differentiation, advanced TNM stage, lymphatic metastasis, and poor prognosis in lung cancer patients. TC1 expression also correlated with β-catenin and DNMT1 expressions. No mutations in C8orf4 were detected. However, methylation levels of C8orf4 in lung cancers were lower than in corresponding normal lung tissues. In conclusion, high TC1 expression is implicated in lung cancer progression and correlates with poor prognosis in lung cancer. Reduced methylation levels might be responsible for the elevated TC1 expression levels. TC1, β-catenin, and DNMT1 can synergistically activate Wnt/β-catenin signaling in lung cancers.
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