Stroma derived COL6A3 is a potential prognosis marker of colorectal carcinoma revealed by quantitative proteomics.
Colorectal cancer (CRC) represents the third most common cancer in males and second in females worldwide. Here, we performed a quantitative 8-plex iTRAQ proteomics analysis of the secreted proteins from five colonic fibroblast cultures and three colon cancer epithelial cell lines. We identified 1114 proteins at 0% FDR, including 587 potential secreted proteins. We further recognized 116 fibroblast-enriched proteins which were significantly associated with cell movement, angiogenesis, proliferation and wound healing, and 44 epithelial cell-enriched proteins. By interrogation of Oncomine database, we found that 20 and 8 fibroblast-enriched proteins were up- and downregulated in CRC, respectively. Western blots confirmed the fibroblast-specific secretion of filamin C, COL6A3, COL4A1 and spondin-2. Upregulated mRNA and stroma expression of COL6A3 in CRC, which were revealed by Oncomine analyses and tissue-microarray-immunohistochemistry, indicated poor prognosis. COL6A3 expression was significantly associated with Dukes stage, T stage, stage, recurrence and smoking status. Circulating plasma COL6A3 in CRC patients was upregulated significantly comparing with healthy peoples. Receiver operating characteristic curve analysis revealed that COL6A3 has better predictive performance for CRC with an area under the curve of 0.885 and the best sensitivity/specificity of 92.9%/81.3%. Thus we demonstrated that COL6A3 was a potential diagnosis and prognosis marker of CRC.
Department of Medical Systems Biology, School of Basic Medical Sciences, Shanghai, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Jie
J
Qiao
Department of Chemistry, Fudan University, Shanghai, China.
Cai-Yun
CY
Fang
Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Sun-Xia
SX
Chen
Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Xiao-Qing
XQ
Wang
College of Bioscience and Biotechnology, Key Laboratory of Crop Genetics and Physiology of Jiangsu Province, Yangzhou University, Yangzhou, China.
Shu-Jian
SJ
Cui
Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Xiao-Hui
XH
Liu
Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Ying-Hua
YH
Jiang
Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Jie
J
Wang
Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Yang
Y
Zhang
Department of Medical Systems Biology, School of Basic Medical Sciences, Shanghai, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, China.|Department of Chemistry, Fudan University, Shanghai, China.
Peng-Yuan
PY
Yang
Department of Medical Systems Biology, School of Basic Medical Sciences, Shanghai, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Feng
F
Liu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D024142:Collagen Type VI / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C000601102:COL6A3 protein, human; D024142:Collagen Type VI; D012333:RNA, Messenger
COL6A3; colorectal cancer; fibroblast; proteomics; tumor microenvironment