Simultaneous measurement of MMP9 and TIMP1 mRNA in human non small cell lung cancers by multiplex real time RT-PCR

Simi, Lisa; Andreani, Matteo; Davini, Federico; Jannì, A; Pazzagli, Mario; Serio, Mario; Orlando, Claudio

doi:10.1016/j.lungcan.2004.01.014

Cited by 34 publications

(14 citation statements)

References 25 publications

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“…Gouyer et al reported TiMP-1 expression to be an indicator of worse prognosis, but this was not related to TNM stage (23). In contrast, Simi et al reported that TiMP-1 expression was related not to patients survival, but rather to nodal spread and metastasis (24). Our results were in accord with those of Simi et al The fact that TIMP-2 was not related to prognosis and disease progression was also in agreement with previous reports (23,25).…”

Section: Discussionsupporting

confidence: 92%

Expression of metastasis-associated molecules in non-small cell lung cancer and their prognostic significance

Lim

Jung²,

Choi³

et al. 2009

Mol Med Rep

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Abstract. Molecules associated with tumor invasion and metastasis have been actively investigated, but their prognostic significance has been variously reported by investigators. We evaluated the expression of matrix metalloproteinase (MMP)-1, MMP-2, MMP-3, MMP-9, MMP-10, tissue inhibitor of MMPs (TiMP)-1, TiMP-2, β-catenin, e-cadherin and cyclooxygenase-2 (coX-2) in 43 cases of non-small cell lung cancer (NSCLC). Immunohistochemistry of each marker was performed on tissue microarray paraffin blocks, and the results were determined by a semi-quantitative method using an intensity score (0-3) and percentage score (0-3). The expression scores of each marker were correlated with TNM stage and patient survival data. The expression of MMP-3 and COX-2 was significantly increased in higher stage tumors (P<0.001 and P=0.046, respectively), while a correlation with patient survival length was observed for MMP-1 and coX-2 (P=0.034 and 0.019, respectively). All stage I or II cases with increased MMP-1 expression succumbed to nSclc within 34.1 months. Cases with low expression of both MMP-1 and COX-2 had a significantly longer survival time than cases with high expression of either of the two markers (P=0.002). These results suggest that MMP-1 and coX-2 are plausible candidate survival markers for NSCLC.

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Section: Discussionsupporting

confidence: 92%

Expression of metastasis-associated molecules in non-small cell lung cancer and their prognostic significance

Lim

Jung²,

Choi³

et al. 2009

Mol Med Rep

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“…Currently, there are more than 20 identified MMPs that can be categorized by substrate specificity. Despite the clinical significance of the pathogenetic impact of MMPs in human cancer, including PCa, only a few studies of MMPs are available in the literature, and those mainly analyze protein expression (18).…”

Section: Discussionmentioning

confidence: 99%

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

et al. 2012

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Prostate cancer (PCa) is a common disease with a multifactorial and complex etiology. It is the most common malignancy in the male and the second leading cause of death in many countries, including Brazil. Estimates for 2011 indicate that 903,500 new cases and 258,400 deaths relatVol. 38 (2): 167-174; March -April, 2012 Objective: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specifi c regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specifi c pattern and if the profi les are related to prognosis and clinical outcome of prostate cancer (PCa). Materials and Methods: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profi le of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the fi nal outcome of the PCa. Results: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (≥ 7) overexpressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). Conclusion: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior. Underexpression of MMP-2 and its

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“…A number of past studies have successfully isolated RNA and protein from tumor samples, and profiled a limited number of MMPs 23-26. For example, protein was successfully extracted from thyroid tumors and relative MMP-1 and MMP-9 measurements were performed using a targeted enzyme linked immunoassay (ELISA) 35.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the absolute changes in MMP profiles with NSCLC which were observed in the present study, are likely the result of altered transcription pathways that are reflective of the underlying cancer process. Indeed, MMP expression profiles have been demonstrated to be directly associated with relevant process of tumor biology which include local growth and prognosis 1,5,7,11,23,25,26. The present study provides for a proof of concept that profiling of a large array of MMPs in NSCLC is possible, and could be expanded to reveal specific subsets of MMPs which hold both diagnostic and therapeutic relevance.…”

Section: Discussionmentioning

confidence: 99%

Differential matrix metalloproteinase levels in adenocarcinoma and squamous cell carcinoma of the lung

Shah

Spinale

Ikonomidis

et al. 2010

The Journal of Thoracic and Cardiovascular Surgery

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Objective The matrix metalloproteinases (MMPs) have been implicated in the aggressive course of non-small cell lung cancer (NSCLC). However, there are a large number of MMP subtypes with diverse proteolytic substrates and different induction pathways. This study tested the hypothesis that a differential MMP profile would exist between NSCLC and normal lung and that MMP patterns would differ between NSCLC histologic type. Methods NSCLC samples and remote normal samples were obtained from patients with stage I or II NSCLC with either squamous cell (n=22) or adenocarcinoma (n=19) histology. Absolute concentrations for each of the MMP subclasses; collagenases (MMP-1, 8, -13), gelatinases (MMP-2,-9), lysins (MMP-2, -7) and elastase (MMP-12) were determined by a calibrated and validated multiplex suspension array. Results Overall, MMP levels were significantly increased in NSCLC compared to normal. For example, MMP-1 and MMP-7 increased by approximately 10 fold in NSCLC (p<0.05). Moreover, a different MMP portfolio was observed between NSCLC histologic types. For example MMP-1,-8,-9 and -12 increased by over 4-fold in squamous cell versus adenocarcinoma (p<0.05). In those patients who recurred within 3 years of resection, 3-fold higher levels of MMP-8 and -9 were observed (p<0.05). Conclusion Increased levels of a number of MMP types occur with NSCLC, but the MMP profile was distinctly different between histologic types and in those patients with recurrence. These different MMP profiles may be important in the mechanistic basis for the natural history of different NSCLC types, as well as identifying potential prognostic and therapeutic targets.

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Simultaneous measurement of MMP9 and TIMP1 mRNA in human non small cell lung cancers by multiplex real time RT-PCR

Cited by 34 publications

References 25 publications

Expression of metastasis-associated molecules in non-small cell lung cancer and their prognostic significance

Expression of metastasis-associated molecules in non-small cell lung cancer and their prognostic significance

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

Differential matrix metalloproteinase levels in adenocarcinoma and squamous cell carcinoma of the lung

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