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World J Gastroenterol. Jan 7, 2011; 17(1): 69-78
Published online Jan 7, 2011. doi: 10.3748/wjg.v17.i1.69
S100A4 over-expression underlies lymph node metastasis and poor prognosis in colorectal cancer
Li-Yong Huang, Ye Xu, Guo-Xiang Cai, Zu-Qing Guan, Wei-Qi Sheng, Hong-Fen Lu, Li-Qi Xie, Hao-Jie Lu, San-Jun Cai
Li-Yong Huang, Ye Xu, Guo-Xiang Cai, Zu-Qing Guan, San-Jun Cai, Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
Li-Yong Huang, Ye Xu, Guo-Xiang Cai, Zu-Qing Guan, Wei-Qi Sheng, Hong-Fen Lu, San-Jun Cai, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Wei-Qi Sheng, Hong-Fen Lu, Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
Li-Qi Xie, Hao-Jie Lu, Department of Chemistry, Fudan University, Shanghai 200032, China
Li-Qi Xie, Hao-Jie Lu, Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China
Author contributions: Huang LY, Xu Y, Cai GX, Guan ZQ, Lu HJ and Cai SJ designed the research; Huang LY and Xie LQ performed the research; Huang LY, Cai GX, Sheng WQ and Lu HF analyzed the data; Huang LY and Cai SJ wrote the paper.
Supported by Shanghai Momentous Program, Grant No. 07dz19505; and Shanghai Rising-star Program from the Science and Technology Commission of Shanghai Municipality, No. 10QA1401400, China
Correspondence to: San-Jun Cai, MD, Professor of Medicine, Chief, Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Shanghai 200032, China. caisanjun@csco.org.cn
Telephone: +86-21-64175590 Fax: +86-21-64035387
Received: April 20, 2010
Revised: August 10, 2010
Accepted: August 17, 2010
Published online: January 7, 2011
AIM: To develop lymph node metastasis (LNM)-associated biomarkers for colorectal cancer (CRC) using quantitative proteome analysis.
METHODS: Differences in protein expression between primary CRC with LNM (LNM CRC) and without LNM (non-LNM CRC) were assessed using methyl esterification stable isotope labeling coupled with 2D liquid chromatography followed by tandem mass spectrometry (2D-LC-MS/MS). The relationship to clinicopathological parameters and prognosis of candidate biomarkers was examined using an independent sample set.
RESULTS: Forty-three proteins were found to be differentially expressed by at least 2.5-fold in two types of CRC. S100A4 was significantly upregulated in LNM CRC compared with non-LNM CRC, which was confirmed by Western blotting, immunohistochemistry and real-time quantitative polymerase chain reaction. Further immunohistochemistry on another 112 CRC cases showed that overexpression of S100A4 frequently existed in LNM CRC compared with non-LNM CRC (P < 0.001). Overexpression of S100A4 was significantly associated with LNM (P < 0.001), advanced TNM stage (P < 0.001), increased 5-year recurrence rate (P < 0.001) and decreased 5-year overall survival rate (P < 0.001). Univariate and multivariate analyses indicated that S100A4 expression was an independent prognostic factor for recurrence and survival of CRC patients (P < 0.05).
CONCLUSION: S100A4 might serve as a powerful biomarker for LNM and a prognostic factor in CRC.
