Proteomic analysis of stromal proteins in different stages of colorectal cancer establishes Tenascin-C as a stromal biomarker for colorectal cancer metastasis

// Maoyu Li 1 , Fang Peng 1 , Guoqing Li 1 , Yang Fu 2 , Ying Huang 1, 3 , Zhuchu Chen 1, 4 , Yongheng Chen 1, 4 1 Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China 2 Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA 3 Maternal and Child Health Hospital of Hunan Province, Changsha, 410008, Hunan Province, China 4 Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China Correspondence to: Zhuchu Chen, email: chenzhuchu@126.com Yongheng Chen, email: yonghenc@163.com Keywords: colorectal carcinoma, multistage carcinogenesis, stromal biomarker, quantitative proteomics, Tenascin-C Received: February 14, 2016 Accepted: April 26, 2016 Published: May 14, 2016 ABSTRACT Tumor microenvironment is crucial to tumor development and metastasis. Little is known about the roles of stromal proteins in colorectal carcinogenesis. In this study, we used a combination of laser capture microdissection (LCM), iTRAQ labeling and two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) to compare stromal proteomes in different stages of colorectal cancer. A total of 1966 proteins were identified, and 222 proteins presenting a significant fold change were quantified in different stages. Differentially expressed proteins (DEPs) were subjected to cluster and pathway analyses. We confirmed the differential expression of Tenascin-C and S100A9 using immunohistochemical analysis, and found that the expression levels of S100A9 and Tenascin-C were correlated with TNM stages and metastasis. In addition, our results showed that Tenascin-C was abundantly secreted by the colon cancer cells with high metastatic potential, and highly expressed in lymph nodes with metastasis. Our studies not only shed light on the mechanism by which stromal proteins contributed to colorectal carcinogenesis, but also identified Tenascin-C as a potential stromal biomarker for colorectal cancer metastasis.