PUBLICATION
Epithelial but not stromal expression of collagen alpha-1(III) is a diagnostic and prognostic indicator of colorectal carcinoma
- Authors
- Wang, X.Q., Tang, Z.X., Yu, D., Cui, S.J., Jiang, Y.H., Zhang, Q., Wang, J., Yang, P.Y., Liu, F.
- ID
- ZDB-PUB-160216-13
- Date
- 2016
- Source
- Oncotarget 7(8): 8823-38 (Journal)
- Registered Authors
- Liu, Feng
- Keywords
- COL3A1, colorectal cancer, prognosis, protein marker
- MeSH Terms
-
- Adult
- Aged
- Aged, 80 and over
- Animals
- Apoptosis
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism*
- Blotting, Western
- Case-Control Studies
- Cell Proliferation
- Collagen Type III/antagonists & inhibitors
- Collagen Type III/genetics
- Collagen Type III/metabolism*
- Colorectal Neoplasms/genetics
- Colorectal Neoplasms/metabolism
- Colorectal Neoplasms/pathology*
- Epithelioid Cells/metabolism*
- Epithelioid Cells/pathology
- Female
- Follow-Up Studies
- Gene Expression Regulation, Neoplastic
- Humans
- Immunoenzyme Techniques
- Male
- Middle Aged
- Neoplasm Grading
- Neoplasm Recurrence, Local/genetics
- Neoplasm Recurrence, Local/metabolism
- Neoplasm Recurrence, Local/pathology*
- Neoplasm Staging
- Prognosis
- RNA, Messenger/genetics
- RNA, Small Interfering/genetics
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Stromal Cells/metabolism*
- Stromal Cells/pathology
- Survival Rate
- Tumor Cells, Cultured
- Xenograft Model Antitumor Assays
- Young Adult
- Zebrafish
- PubMed
- 26741506 Full text @ Oncotarget
Citation
Wang, X.Q., Tang, Z.X., Yu, D., Cui, S.J., Jiang, Y.H., Zhang, Q., Wang, J., Yang, P.Y., Liu, F. (2016) Epithelial but not stromal expression of collagen alpha-1(III) is a diagnostic and prognostic indicator of colorectal carcinoma. Oncotarget. 7(8):8823-38.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping