title: Upregulation of spondin-2 predicts poor survival of colorectal carcinoma patients.
abstract: Colorectal cancer (CRC) is the third and second most common cancer in males and females worldwide, respectively. Spondin-2 is a conserved secreted extracellular matrix protein and a candidate cancer biomarker. Here we found that Spondin-2 mRNA was upregulated in CRC tissues using quantitative RT-PCR and data-mining of public Oncomine microarray datasets. Spondin-2 protein was increased in CRC tissues, as revealed by immunohistochemistry analyses of two tissue microarrays containing 180 cases. Spondin-2 gene expression was significantly associated with CRC stage, T stage, M stage and Dukes stage, while its protein was associated with age and M stage. Kaplan-Meier analysis revealed that the upregulated Spondin-2 mRNA and protein predicted poor prognosis of CRC patients. Univariate and multivariate Cox regression analyses indicated that grade, recurrence, N stage and high Spondin-2 were independent predictors of overall survival of CRC patients. ELISA revealed that plasma Spondin-2 was upregulated in CRC and dropped after surgery. Receiver operating characteristic curve analysis demonstrated that plasma Spondin-2 has superior predictive performance for CRC with an area under the curve of 0.959 and the best sensitivity/specificity of 100%/90%. Furthermore, ectopic expression of Spondin-2 enhanced colon cancer cell proliferation. Spondin-2 could be an independent diagnostic and prognostic biomarker of colon cancer.
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.|Department of Chemistry, Fudan University, Shanghai, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Bioscience and Biotechnology, Key Laboratory of Crop Genetics and Physiology of Jiangsu Province, Yangzhou University, Yangzhou, Jiangsu, China.
authors.forename: Shu-Jian
authors.initials: SJ
authors.lastname: Cui
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Chaoyang District, Beijing, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Lou
authors.affiliation: Key Laboratory of Digestive Organ Transplantation of Henan Province and the Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Jiang
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Jinshan District, Shanghai, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.|Department of Chemistry, Fudan University, Shanghai, China.
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Yang
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.|Minhang Hospital, Fudan University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western / Q000706:statistics & numerical data; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000706:statistics & numerical data; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; C122166:SPON2 protein, human
keywords: SPON2; colorectal cancer; prognosis; protein marker; spondin-2