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Oncotarget. 2016 Dec 13;7(50):82609-82619. doi: 10.18632/oncotarget.12089.

Positive association of collagen type I with non-muscle invasive bladder cancer progression.

Author information

1
Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.
2
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
3
Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
4
Department of Urology, Baylor College of Medicine, Kelsey-Seybold Clinic, Houston, Texas 77030, USA.
5
Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
6
Department of Pathology and Immunology, and Michael E. DeBakey VAMC, Baylor College of Medicine, Houston, Texas 77030, USA.
7
Center for Cell, Gene and Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
8
Center for Drug Discovery Baylor College of Medicine, Houston, Texas 77030, USA.

Abstract

PURPOSE:

Non-muscle invasive bladder cancers (NMIBC) are generally curable, while ~15% progresses into muscle-invasive cancer with poor prognosis. While efforts have been made to identify genetic alternations associated with progression, the extracellular matrix (ECM) microenvironment remains largely unexplored. Type I collagen is a major component of the bladder ECM, and can be altered during cancer progression. We set out to explore the association of type I collagen with NMIBC progression.

EXPERIMENTAL DESIGN:

The associations of COL1A1 and COL1A2 mRNA levels with progression were evaluated in a multi-center cohort of 189 patients with NMIBCs. Type I collagen protein expression and structure were evaluated in an independent single-center cohort of 80 patients with NMIBCs. Immunohistochemical analysis was performed and state-of-the-art multi-photon microscopy was used to evaluate collagen structure via second harmonic generation imaging. Progression to muscle invasion was the primary outcome. Kaplan-Meier method, Cox regression, and Wilcoxon rank-sum were used for statistical analysis.

RESULTS:

There is a significant association of high COL1A1 and COL1A2 mRNA expression in patients with poor progression-free survival (P=0.0037 and P=0.011, respectively) and overall survival (P=0.024 and P=0.012, respectively). Additionally, immunohistochemistry analysis of type I collagen protein deposition revealed a significant association with progression (P=0.0145); Second-harmonic generation imaging revealed a significant lower collagen fiber curvature ratio in patients with invasive progression (P = 0.0018).

CONCLUSIONS:

Alterations in the ECM microenvironment, particularly type I collagen, likely contributes to bladder cancer progression. These findings will open avenues to future functional studies to investigate ECM-tumor interaction as a potential therapeutic intervention to treat NMIBCs.

KEYWORDS:

bladder cancer; cancer progression; invasion; tumor microenvironment; type I collagen

PMID:
27655672
PMCID:
PMC5347718
DOI:
10.18632/oncotarget.12089
[Indexed for MEDLINE]
Free PMC Article

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