Overexpression of Collagen Triple Helix Repeat Containing 1 (CTHRC1) is associated with tumour aggressiveness and poor prognosis in human non-small cell lung cancer

// Zunfu Ke 1, * , Weiling He 2, * , Yuanhui Lai 3, * , Xuefeng Guo 4 , Sharon Chen 5 , Shuhua Li 1 , Yuefeng Wang 1 , Liantang Wang 1 1 Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 2 Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 3 Vascular and Thyroid Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 4 Department of Gastrointestinal Surgery, the Sixth Affliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 5 Department of Molecular and Medical Pharmacology, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA USA * These authors contributed equally to this work. Correspondence to: Dr. Zunfu ke, e-mail: kezunfu@mail.sysu.edu.cn Dr. Liantang Wang, e-mail: wanglt@mail.sysu.edu.cn Keywords: CTHRC1 non-small cell lung cancer β-catenin metastasis prognosis Received: August 04, 2014      Accepted: August 28, 2014      Published: September 24, 2014 ABSTRACT Collagen triple helix repeat-containing 1 (CTHRC1), a novel oncogene, was identified to be aberrantly overexpressed in several malignant tumors. However, the expression profile of CTHRC1 and its clinical significance in non-small cell lung cancer (NSCLC) remain unknown. In this study, we showed that CTHRC1 was evidently overexpressed in human NSCLC tissues and NSCLC cell lines at the protein and mRNA level. Ectopic up-regulation of CTHRC1 in cancer cells resulted in elevated invasive and proliferative abilities, which were attenuated by the specific CTHRC1 siRNA. The biological effect of CTHRC1 on metastasis and proliferation was mediated by the activation of the Wnt/β-catenin pathway. Furthermore, CTHRC1 immunoreactivity was evidently overexpressed in paraffin-embedded NSCLC tissues (212/292, 72.60%) in comparison to corresponding adjacent non-cancerous tissues (6/66, 9.09%) ( p <0.001). Clinicopathologic analysis showed that CTHRC1 expression was significantly correlated with differentiation degree ( p <0.001), clinical stage ( p <0.001), T classification ( p <0.001), lymph node metastasis ( p =0.013) and distant metastasis ( p <0.001). Kaplan-Meier analysis revealed that patients with high CTHRC1 expression had poorer overall survival rates than those with low CTHRC1 expression. Multivariate analysis indicated that CTHRC1 expression was an independent prognostic factor for the overall survival of NSCLC patients. Collectively, CTHRC1 plays important roles in NSCLC progression, and the evaluation of CTHRC1 expression could serve as a potential marker for metastasis progression and prognosis in NSCLC patients.