Epithelial but not stromal expression of collagen alpha-1(III) is a diagnostic and prognostic indicator of colorectal carcinoma

Wang, X.Q., Tang, Z.X., Yu, D., Cui, S.J., Jiang, Y.H., Zhang, Q., Wang, J., Yang, P.Y., Liu, F.
Oncotarget   7(8): 8823-38 (Journal)
Registered Authors
Liu, Feng
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
26741506 Full text @ Oncotarget
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
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes