Matrix metalloproteinases (MMPs) and inhibitor of metalloproteinases (TIMP) mRNA and protein expression in laryngeal squamous cell carcinoma.

INTRODUCTION: The aim of the study was to investigate the mRNA expression and protein levels of matrix metalloproteinases (MMP) 2 (MMP-2), 9 (MMP-9), 7 (MMP-7) and their tissue inhibitor TIMP-2 in patients with laryngeal squamous cell carcinoma and control subjects and additionally to evaluate a possible correlation with clinicopathological features. MATERIAL AND METHODS: The expression levels of MMP-2, MMP-9, MMP-7, and TIMP-2 mRNA were detected by the real-time quantitative real time polymerase chain reaction method in 96 cases of laryngeal carcinoma vs. non-tumor tissue. The blood serum levels of MMP-2, MMP-9, MMP-7, and TIMP-2 in patients with laryngeal cancer and 100 healthy subjects were measured using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The present study demonstrated that MMP-2, MMP-7, MMP-9 and TIMP-2 mRNA expression levels in carcinoma tissue vs. non-tumor tissue and protein levels in the preoperative serum vs. those obtained in healthy controls were statistically significantly higher than in the healthy controls (p = 0.001). The only significant correlation between mRNA or concentration of measured MMPs and TIMP and the clinicopathological features was found for TIMP-2 protein and for patients with lymph node metastasis. Serum levels of TIMP-2 were higher in cases with lymph node metastasis than in those without lymph node metastasis (p < 0.05). CONCLUSIONS: The results may suggest that MMPs and TIMP-2 are associated with laryngeal tumorigenesis, but we did not find any distinct correlation between the clinicopathological features of laryngeal squamous cell carcinoma patients and expression levels of MMPs and TIMP. The results suggest that the measurement of serum MMP-2, MMP-7, MMP-9 and TIMP-2 concentration might be helpful to diagnose laryngeal squamous cell carcinoma.

The matrix metalloproteinase in larynx cancer.

One of the most common carcinoma occurring in the head and neck is laryngeal cancer. Despite the rapid scientific advances in medicine the prognosis for patients with such type of disease is not satisfying. In the last few years matrix metalloproteinases ­ MMPs and their tissue inhibitors - TIMPs, mostly MMP­2 and MMP­9, arouses a great interest, especially in the process of carcinogenesis. It seems that their impact in the formation and development of laryngeal cancer is significant. MMPs a group of zinc­ and calcium­ dependent endopeptidases play crucial role extracellular matrix collagen degradation. That are enzymes, that degrade and the basement membrane by facilitating tumor growth, cell migration and tumor invasion. They are implicated in metastasis and angiogenesis potentiate within the tumor. Clear tendency was observed towards the higher MMPs and TIMPs expression in larynx cancer than in the stroma. Recent studies show correlations between increased MMP­2 gene expression in the tumor tissue and clinical status, histopathological grading and metastases occurrence. The similar MMP2 over expression dependence were found on tumor recurrence and survival. Many authors pointed out, significant higher MMP­2 expression as a potential marker of tumor invasiveness and worse prognosis in patients with larynx cancer. However, association of MMP 9 gene expression with laryngeal cancer clinicopathological features and survival of patients are ambiguous. Although, numerous researches show that this relationship does exists. Similar correlations could be found in TIMPs, but further studies are necessary because of small amount of literature.

New miRNA expression abnormalities in laryngeal squamous cell carcinoma.

BACKGROUND: Although the development of novel diagnostic and treatment strategies concerning laryngeal cancer is highly intensive, the survival rate remains virtually unchanged. Small non-coding RNAs appear to be very promising biomarkers - and so remain the focus of extensive investigation in laryngeal cancer. OBJECTIVE: We examined the expression of five miRNA and five genes related to cancer whether they could be potential laryngeal cancer biomarkers. METHODS: We performed an analysis in 47 patients diagnosed with laryngeal cancer. The qPCR technique was used to investigate the expression profile. RESULTS: While miR-21-3p and miR-525-5p were found to be significantly up-regulated, miR-139-3p and miR-885-5p expression is lower in laryngeal cancer. Moreover, PIK3R1 and HACE1 were found to be also down-regulated. CONCLUSIONS: The change in miRNA expression is frequent than the expression of other tested genes. The expression of passenger strands such as miR-21-3p and miR-139-3p, which are rarely investigated, is also significantly affected in laryngeal cancer. While PIK3R1, HACE1, miR-139-3p, and miR-885-5p may act as tumor suppressor genes in the studied tumour type, miR-21-3p and miR-525-5p seem to have oncogenic properties. Our findings suggest that miR-885-5p and PIK3R1 are the best indicators for the classification of laryngeal cancer tissue and normal mucosa.