MMP, VEGF and TIMP as prognostic factors in recurring bladder cancer

Wieczorek, Edyta; Jabłonowski, Zbigniew; Tomasik, Bartłomiej; Konecki, Tomasz; Jabłońska, Ewa; Gromadzińska, Jolanta; Fendler, Wojciech; Sosnowski, Marek; Wąsowicz, Wojciech; Reszka, Edyta

doi:10.1016/j.clinbiochem.2015.07.021

Cited by 20 publications

(11 citation statements)

References 29 publications

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“…In cancer, MMP-9 is associated with genetic instability, tissue remodeling, tumor cell proliferation, invasion and motility, progression, extravasation, metastasis, epithelial-mesenchymal transition, angiogenesis, apoptosis, inflammation, and immunosurveillance (36). MMP-9 in PBLs, serum, and tumors predicts prognosis, invasiveness, grade and differentiation, recurrence, metastasis, and treatment resistance, for bladder, lung, blood, colorectal, prostate, and liver cancers (42)(43)(44)(45)(46)(47)(48)(49). In patients with RCC, MMP-9 is increased in tumors and plasma (50) and correlates with histological grade (51), poor prognosis, and lowered survival (52), metastasis, decreased time to progression, and poor response to sunitinib (53).…”

Section: Discussionmentioning

confidence: 99%

Failed immune responses across multiple pathologies share pan-tumor and circulating lymphocytic targets

Monette

Morou

Al-Banna

et al. 2019

Journal of Clinical Investigation

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Figure 1. Distinct comprehensive transcriptomics from paired CD8 + and CD19 + profiles from ccRCC blood, tumors and tissues, and control donor blood isolates. (A and B) PCA demonstrating distinct DEG profiles from comprehensive HTA 2.0 microarray analyses of (A) CD8 + (n = 15) and (B) CD19 + (n = 15) immune cell subsets from TILs and TIL-Bs, TIICs, and circulating ptPBLs, and cdPBLs (n = 10). (C) Four-way Venn diagram demonstrating percentage overlaps of DEGs identified by microarrays across different source biospecimens analyzed. (D) Venn diagram showing that ptPBLs have greater numbers of differentially represented exon-exon PSR junctions compared with TILs, relative to TIICs from paired CD8 + samples (P < 0.05; ANOVA, Transcriptome Analysis Console v.3, Affymetrix). Thirteen percent of shared PSR junctions exist between ptPBLs and TILs, representing 33% of total genes common to ptPBLs and TILs having shared isoform identity. (E) GO PM proteins identified by Partek and unsupervised hierarchical clustering algorithm-generated heatmaps demonstrating that the 4 different CD8 + isolates are stratified according to PM, using log 2 expression values applying the Euclidean distance metric and complete linkage clustering method (R programming language; R-studio). Heatmaps demonstrate the unsupervised clustering of PBL isolates as most closely related, with TILs and TIICs at their boundaries, suggesting that their profiles may be influenced by the cancer microenvironment. (F) Feasibility of using PM-associated proteins toward identifying pan-cancer DEGs that can stratify patients is demonstrated by PCA biplots of PM DEGs from CD8 + cdPBL and ptPBL isolates created on log 2 values using the biplot function (R; R-studio). diff., differential; id., identity; PSR, probe-selected region.

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Section: Discussionmentioning

confidence: 99%

Failed immune responses across multiple pathologies share pan-tumor and circulating lymphocytic targets

Monette

Morou

Al-Banna

et al. 2019

Journal of Clinical Investigation

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“…Meta-analysis has been done to evaluate prognostic significance of high MMPs expression; nevertheless, correlation between bladder tumor progression/ metastasis and overexpression of MMPs is still debatable [17]. Enhanced migratory and invasive capacity of MMPs and their involvement in neoplastic transformation, probably through aberrant downstream activation of EMT, makes them an ideal candidate to evaluate their diagnostic and prognostic relevance in two distinct types of bladder cancer disease [18]. The objective of the current study is to examine the downstream activation of EMT programs as a consequence of increased expression of specific MMPs and their clinical utility in early stages of bladder carcinogenesis and tumor invasion.…”

Section: Introductionmentioning

confidence: 99%

Positive Correlation between Matrix Metalloproteinases and Epithelial-to-Mesenchymal Transition and its Association with Clinical Outcome in Bladder Cancer Patients

Singh

Mandhani

Agrawal

et al. 2018

Cancer Microenvironment

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Involvement of matrix metalloproteinases (MMPs) in the pathogenesis of urothelial carcinoma elects them to be sensitive marker for clinical and prognostic implications. MMPs regulate tumor growth and invasion by inducing epithelial-to-mesenchymal transition (EMT) which is characterized by the complex reprogramming of epithelial cells and ultimately bring about major changes in the structural organization of bladder urothelium. The present study has been undertaken to evaluate the clinical relevance of MMPs in two distinct types of bladder cancer disease. Expression analysis of MMPs namely MMP-2, MMP-7, MMP-9 and EMT markers including epithelial marker, E-cadherin; mesenchymal markers, N-cadherin and Vimentin; and EMT-activating transcriptional factors (EMT-ATFs), Snail, Slug, Twist and Zeb was done in 64 cases of bladder tumor tissues [{Non-muscle invasive bladder cancer (NMIBC): 35 cases} and {Muscle invasive bladder cancer (MIBC): 29 cases}] by real-time quantitative polymerase chain reaction (RT-qPCR). Immunohistochemistry (IHC) staining was done in matched bladder tumor tissues to evaluate the protein expression and localization of E-cadherin, N-cadherin, Vimentin, Snail, and Slug. Our data showed overexpression of MMP-2, MMP-7 and MMP-9 at transcriptome level in 32.8%, 25% and 37.5% bladder tumor cases respectively. These tumor tissues were examined for higher expression of mesenchymal markers (N-cadherin and Vimentin) at mRNA and protein level and exhibited statistical association with tumor stage and tumor grade (p = 0.02, p = 0.04, Mann-Whitney test). Significant statistical correlation in tumor tissues with overexpressed MMPs has also been observed between gain of transcriptional factors and weak expression of E-cadherin with tumor stage, grade, gender, presence of hematuria and smoking history of the patients. Gene expression patterns of EMT markers in bladder tumors with overexpressed MMPs and their significant association with clinical profile validate the important role of MMPs in the pathogenesis of urothelial carcinoma of bladder (UCB). Increased expression of specific MMPs may affect several downstream EMT programs and thus may improve its diagnostic and prognostic utility in clinical setting.

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“…We have measured levels of urinary and plasma VEGF-A in the same study population. While VEGF-A was already described as a component of variety of multi-marker diagnostic tests and its prognostic value in bladder cancer patients was reported, no study evaluating PLGF as a diagnostic or prognostic marker of bladder cancer has been published to date (18)(19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

Placental Growth Factor in Bladder Cancer Compared to the Diagnostic Accuracy and Prognostic Performance of Vascular Endothelial Growth Factor A

Soukup

Čapoun

Pešl

et al. 2018

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MMP, VEGF and TIMP as prognostic factors in recurring bladder cancer

Cited by 20 publications

References 29 publications

Failed immune responses across multiple pathologies share pan-tumor and circulating lymphocytic targets

Failed immune responses across multiple pathologies share pan-tumor and circulating lymphocytic targets

Positive Correlation between Matrix Metalloproteinases and Epithelial-to-Mesenchymal Transition and its Association with Clinical Outcome in Bladder Cancer Patients

Placental Growth Factor in Bladder Cancer Compared to the Diagnostic Accuracy and Prognostic Performance of Vascular Endothelial Growth Factor A

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