title: Overexpression of collagen triple helix repeat containing 1 (CTHRC1) is associated with tumour aggressiveness and poor prognosis in human non-small cell lung cancer.
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.
authors.affiliation: Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R. China. These authors contributed equally to this work.
authors.forename: Zunfu
authors.initials: Z
authors.lastname: Ke
authors.affiliation: Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R. China. These authors contributed equally to this work.
authors.forename: Weiling
authors.initials: W
authors.lastname: He
authors.affiliation: Vascular and Thyroid Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R. China. These authors contributed equally to this work.
authors.forename: Yuanhui
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Department of Gastrointestinal Surgery, the Sixth Affliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510655.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095-1770 (USA).
authors.forename: Sharon
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R. China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R. China.
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R. China.
authors.forename: Liantang
authors.initials: L
authors.lastname: Wang
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C502426:CTHRC1 protein, human; D016326:Extracellular Matrix Proteins; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3