Dataset Information

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

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.

SUBMITTER: Brooks M

PROVIDER: S-EPMC5347718 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Brooks Michael M Mo Qianxing Q Krasnow Ross R Ho Philip Levy PL Lee Yu-Cheng YC Xiao Jing J Kurtova Antonina A Lerner Seth S Godoy Gui G Jian Weiguo W Castro Patricia P Chen Fengju F Rowley David D Ittmann Michael M Chan Keith Syson KS

Oncotarget 20161201 50

<h4>Purpose</h4>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 progress ...[more]

PMID: 27655672

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Project description:BackgroundNon-muscle invasive bladder neoplasms with invasion of the lamina propria (stage T1) or high grade of dysplasia are at "high risk" of progression to life-threatening cancer. However, the individual course is difficult to predict. Chromosomal instability (CI) is associated with high tumor stage and grade, and possibly with the risk of progression.MethodsTo investigate the relationship between CI and subsequent disease progression, we performed a case-control-study of 125 patients with "high-risk" non-muscle invasive bladder neoplasms, 67 with later disease progression, and 58 with no progression. Selection criteria were conservative (non-radical) resections and full prospective clinical follow-up (> 5 years). We investigated primary lesions in 59, and recurrent lesions in 66 cases.We used Affymetrix GeneChip Mapping 10 K and 50 K SNP microarrays to evaluate genome wide chromosomal imbalance (loss-of-heterozygosity and DNA copy number changes) in 48 representative tumors. DNA copy number changes of 15 key instability regions were further investigated using QPCR in 101 tumors (including 25 tumors also analysed on 50 K SNP microarrays).ResultsChromosomal instability did not predict any higher risk of subsequent progression. Stage T1 and high-grade tumors had generally more unstable genomes than tumors of lower stage and grade (mostly non-primary tumors following a "high-risk" tumor). However, about 25% of the "high-risk" tumors had very few alterations. This was independent of subsequent progression. Recurrent lesions represent underlying field disease. A separate analysis of these lesions did neither reflect any difference in the risk of progression. Of specific chromosomal alterations, a possible association between loss of chromosome 8p11 and the risk of progression was found. However, the predictive value was limited by the heterogeneity of the changes.ConclusionChromosomal instability (CI) was associated with "high risk" tumors (stage T1 or high-grade), but did not predict subsequent progression. Recurrences after "high-risk" tumors had fewer chromosomal alterations, but there was no association with the risk of progression in this group either. Thus, the prediction of progression of "high risk" non-muscle invasive bladder tumors using chromosomal changes is difficult. Loss of chromosome 8p11 may play a role in the progression process. About 25% of the "high risk" tumors were chromosomal stable.

Dataset Information

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

Purpose

Experimental design

Results

Conclusions

Publications

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

Similar Datasets

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