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

Michael Brooks, Qianxing Mo, Ross Krasnow, Philip Levy Ho, Yu Cheng Lee, Jing Xiao, Antonina Kurtova, Seth Lerner, Gui Godoy, Weiguo Jian, Patricia Castro, Fengju Chen, David Rowley, Michael Ittmann, Keith Syson Chan

研究成果: 雜誌貢獻文章同行評審

56 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)82609-82619
頁數11
期刊Oncotarget
7
發行號50
DOIs
出版狀態已發佈 - 2016
對外發佈

ASJC Scopus subject areas

  • 腫瘤科

指紋

深入研究「Positive association of collagen type I with non-muscle invasive bladder cancer progression」主題。共同形成了獨特的指紋。

引用此