title: Epithelial but not stromal expression of collagen alpha-1(III) is a diagnostic and prognostic indicator of colorectal carcinoma.
abstract: Colorectal cancer (CRC) is the third most common cancer in males and the second in females worldwide with very poor prognosis. Collagen alpha-1(III) (COL3A1) gene, encoding an extracellular matrix protein, is upregulated in human cancers. Here, we revealed that COL3A1 was increased in CRC by analysis of five Oncomine gene expression datasets (n = 496). Immunohistochemistry analysis of a tissue microarray (n = 90) demonstrated that cancer epithelial but not stromal COL3A1 was significantly upregulated comparing with the normal counterparts. High COL3A1 mRNA and/or protein expression was accompanied with high stage, T stage, Dukes stage, grade and older age, as well as smoking and recurrence status. Upregulated COL3A1 predicted poor overall (p = 0.003) and disease-free (p = 0.025) survival. Increased epithelial but not stromal COL3A1 protein predicted worse outcome (p = 0.03). Older patients (age>65) with high COL3A1 had worse survival than younger (age≤65) with high COL3A1. Plasma COL3A1 was increased in CRC patients (n = 86) by 5.4 fold comparing with healthy individuals, enteritis and polyps patients. Plasma COL3A1 had an area under curve (AUC) of 0.92 and the best sensitivity/specificity of 98.8%/69.1%. While plasma CEA had a poorer prediction power (AUC = 0.791, sensitivity/selectivity = 70.2%/73.0%). Older patients (age≥60) had higher plasma COL3A1 than younger patients. The epithelial COL3A1 protein had an AUC of 0.975 and the best sensitivity/specificity of 95.2%/91.1%. Silencing of COL3A1 suppressed CRC cell proliferation in in vitro MTT assay and in in vivo Zebra fish xenograft model by downregulation of PI3K/AKT and WNT signaling. COL3A1 was a novel diagnosis and prognosis marker of CRC.
authors.affiliation: Department of Systems Biology for Medicine of 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 General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Zu-Xiong
authors.initials: ZX
authors.lastname: Tang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yu
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: Department of Systems Biology for Medicine of 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: Department of Systems Biology for Medicine of 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 of 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: Department of Systems Biology for Medicine of 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 of 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: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D024061:Collagen Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015622:Epithelioid Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult; D015027:Zebrafish
chemical_list: D014408:Biomarkers, Tumor; C439971:COL3A1 protein, human; D024061:Collagen Type III; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: COL3A1; colorectal cancer; prognosis; protein marker