Positive association of collagen type I with non-muscle invasive bladder cancer progression.
Positive association of collagen type I with non-muscle invasive bladder cancer progression.
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DOI：
10.18632/oncotarget.12089
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发表时间：
2016-12-13
期刊：
影响因子：
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通讯作者：
Chan KS
中科院分区：
文献类型：
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作者：
Brooks M;Mo Q;Krasnow R;Ho PL;Lee YC;Xiao J;Kurtova A;Lerner S;Godoy G;Jian W;Castro P;Chen F;Rowley D;Ittmann M;Chan KS
非肌层浸润性膀胱癌（NMIBC）通常是可治愈的，而~15%的患者会发展为肌层浸润性癌症，预后不良。虽然已经努力鉴定与进展相关的遗传改变，但细胞外基质（ECM）微环境仍然在很大程度上未被探索。I型胶原蛋白是膀胱ECM的主要成分，并且可以在癌症进展期间改变。我们着手探讨I型胶原与NMIBC进展的相关性。在189例NMIBC患者的多中心队列中评估了COL1A1和COL1A2 mRNA水平与进展的相关性。I型胶原蛋白的表达和结构进行了评估，在一个独立的单中心队列的80例NMIBC患者。进行免疫组织化学分析，并使用最先进的多光子显微镜通过二次谐波成像评价胶原结构。进展为肌肉浸润是主要结局。采用Kaplan-Meier法、考克斯回归和Wilcoxon秩和进行统计学分析。COL1A1和COL1A2 mRNA的高表达与患者的无进展生存期（分别为P = 0.0037和P = 0.011）和总生存期（分别为P = 0.024和P = 0.012）显著相关。此外，I型胶原蛋白沉积的免疫组化分析显示与进展显著相关（P = 0.0145）;二次谐波成像显示浸润性进展患者的胶原纤维曲率比显著降低（P = 0.0018）。ECM微环境的改变，特别是I型胶原蛋白，可能有助于膀胱癌的进展。这些发现将为未来的功能研究开辟道路，以研究ECM-肿瘤相互作用作为治疗NMIBC的潜在治疗干预。
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. 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. 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). 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.