Upregulation of spondin-2 predicts poor survival of colorectal carcinoma patients
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Qian Zhang1,*, Xiao-Qing Wang1,2,*, Jie Wang1, Shu-Jian Cui5, Xiao-Min Lou6, Bing Yan7, Jie Qiao1, Ying-Hua Jiang1, Li-Jun Zhang4, Peng-Yuan Yang1,2 and Feng Liu1,3
1 Department of Systems Biology for Medicine, School of Basic Medical Sciences, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
2 Department of Chemistry, Fudan University, Shanghai, China
3 Minhang Hospital, Fudan University, Shanghai, China
4 Shanghai Public Health Clinical Center, Fudan University, Jinshan District, Shanghai, China
5 College of Bioscience and Biotechnology, Key Laboratory of Crop Genetics and Physiology of Jiangsu Province, Yangzhou University, Yangzhou, Jiangsu, China
6 CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Chaoyang District, Beijing, China
7 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
* These authors have contributed equally to this work
Feng Liu, email:
Peng-Yuan Yang, email:
Keywords: colorectal cancer, SPON2, spondin-2, prognosis, protein marker
Received: December 10, 2014 Accepted: March 29, 2015 Published: April 14, 2015
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.
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