title: Differential expression of CCN family members CYR611, CTGF and NOV in gastric cancer and their association with disease progression.
abstract: CCN is an acronym for cysteine-rich protein 61 (CYR61), connective tissue growth factor (CTGF) and nephroblastoma overexpressed (NOV). Aberrations of certain CCN members including CYR61, CTGF, Wnt1-inducible signalling pathway protein (WISP)-1 and -3 have been reported in gastric cancer. The present study aimed to examine the clinical relevance of NOV along with CYR61 and CTGF in gastric cancer by analysing their transcript levels. CYR61, CTGF and NOV transcript expression in 324 gastric cancer samples with paired adjacent normal gastric tissues were determined using real-time quantitative PCR and the results were statistically analysed against patient clinicopathological data using SPSS software. NOV mRNA levels in gastric cancer tissues were significantly elevated when compared with levels in their paired adjacent non-cancerous tissues. Local advanced tumours with invasive expansion (T3 and T4) expressed higher levels of NOV (p=0.013) compared with the less invasive tumours (T1 and T2). CYR61 transcript levels were also significantly increased in gastric cancers compared with levels in the adjacent non-cancerous tissues. Kaplan-Meier survival curves revealed that patients with CYR61-low transcript levels had longer overall survival (OS) (p=0.018) and disease-free survival (DFS) (p=0.015). NOV overexpression promoted the in vitro proliferation of AGS cells while the knockdown resulted in a reduced proliferation of HGC27 cells. A similar effect was observed for the invasion of these two gastric cancer cell lines. NOV expression was increased in gastric cancer which was associated with local invasion and distant metastases. Taken together, the expression of NOV and CYR61 was increased in gastric cancer. The elevated expression of CYR61 was associated with poorer survival. NOV promoted proliferation and invasion of gastric cancer cells. Further investigations may highlight their predictive and therapeutic potential in gastric cancer.
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, Xi-Cheng, Beijing 100050, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Gao
authors.affiliation: Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Ke
authors.initials: K
authors.lastname: Ji
authors.affiliation: Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sanders
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, Xi-Cheng, Beijing 100050, P.R. China.
authors.forename: Zhongtao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Chinese Ministry of Education), Department of GI Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Ji
authors.affiliation: Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D055515:Cysteine-Rich Protein 61 / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009367:Neoplasm Staging; D055514:Nephroblastoma Overexpressed Protein / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C501848:CCN1 protein, human; C526317:CCN2 protein, human; C526319:CCN3 protein, human; D055515:Cysteine-Rich Protein 61; D055514:Nephroblastoma Overexpressed Protein; D055513:Connective Tissue Growth Factor