Increased expression of MMP14 correlates with the poor prognosis of Chinese patients with gastric cancer

doi:10.1016/j.gene.2015.03.003

Gene

Volume 563, Issue 1, 25 May 2015, Pages 29-34

https://doi.org/10.1016/j.gene.2015.03.003 Get rights and content

Highlights

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MMP14 mRNA and protein expression are increased in gastric cancer tissues.
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MMP14 expression correlated with the malignant status in gastric cancer patients.
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MMP14 is an independent prognostic factor for patients with gastric cancer.

Abstract

The role of matrix metalloproteinase 14 (MMP14) has been identified to involve tumor progression and prognosis. The purpose of this study is to investigate the role of MMP14 in tumor progression and prognosis of gastric cancer. This study indicated that MMP14 mRNA and protein were overexpressed in gastric cancer tissue (P < 0.001 and P = 0.037, respectively) and significantly associated with clinical stage (P = 0.005), lymph node metastasis (P = 0.003), and distant metastasis (P = 0.017). Moreover, we found that the overexpression of MMP14 was a significant predictor of poor prognosis for gastric cancer patients (P < 0.001). Furthermore, we performed a meta-analysis which included 594 cases from 3 studies and showed that MMP14 overexpression was a significantly poor prognostic factor in Chinese patients with gastric cancer and HR (95% CI) was 2.17 (1.64–2.86). In conclusion, MMP14 plays an important role on gastric cancer progression and prognosis and acts as a convictive biomarker for prognostic prediction for Chinese patients with gastric cancer.

Introduction

Gastric cancer is the second leading cause of cancer-related death, and is the most common gastrointestinal malignancy in East Asia, Eastern Europe, and parts of Central and South America (Ferlay et al., 2010, Siegel et al., 2014). Because of the lack of early specific symptoms, most patients with gastric cancer tend to present with an advanced stage of disease at the time of diagnosis. Although recent advances in the diagnosis, progress in surgical techniques and the development of new chemotherapeutic regimens have reduced gastric cancer deaths, the prognosis of advanced gastric cancer patient is still poor (Shi and Zhou, 2010). The identification of biomarkers for gastric cancer progression and prognosis is imminently needed.

Matrix metalloproteinase-14 (MMP14) was the first membrane type matrix metalloproteinase discovered, and hence is also referred to as membrane type 1-matrix metalloproteinase (MT1-MMP). MMP14 has been suggested to involve in many biological processes, such as proliferation, invasion, angiogenesis, and basement membrane remodeling (Pahwa et al., 2014). Generally, MMPs are produced by tissues as inactive zymogens and require further activation. However, MMP14 does not require additional activation, due to its capacity to be presented on the cell membrane in its active form (Itoh and Seiki, 2006). The present study demonstrated that the expression and the activity of MMP14 are elevated in tumor cells, and high levels of MMP14 directly correlate with enhanced cell migration (Strongin, 2010).

The aim of this study was to identify the pathological roles of MMP14 in gastric cancer. This study indicated that MMP14 mRNA and protein were overexpressed in gastric cancer tissue and significantly associated with clinical stage, lymph node metastasis, and distant metastasis. Moreover, we found that the overexpression of MMP14 was a significant predictor of poor prognosis for gastric cancer patients. Furthermore, we performed a meta-analysis which included 594 cases from 3 studies and showed that MMP14 overexpression was a significantly poor prognostic factor in Chinese patients with gastric cancer and HR (95% CI) was 2.17 (1.64–2.86).

Section snippets

Sample collection

Twenty fresh gastric cancer samples and twenty fresh paired adjacent normal gastric samples were collected from Laiwu People's Hospital. All fresh samples were immediately preserved in liquid nitrogen. Two hundred and five paraffin-embedded gastric cancer samples and thirty two normal gastric epithelial samples were retrieved from Laiwu People's Hospital. No patients had received relevant tumor therapy before diagnosis. Before the use of these clinical samples, prior consents from the patients

MMP14 is expressed at high levels in gastric cancer

Real time-PCR analysis indicated that the MMP14 mRNA expression level was significantly increased in gastric cancer tissues compared to normal gastric tissues (P < 0.001, Fig. 1). We also measured the expression levels of MMP14 protein in archived paraffin-embedded gastric cancer samples and normal gastric tissues using immunohistochemical staining (Fig. 2). MMP14 protein was highly expressed in normal gastric cancer tissues compared to normal gastric tissues (P = 0.037, Table 1).

High protein expression of MMP14 was associated with gastric cancer progression and poor prognosis

We next analyzed

Discussion

Matrix metalloproteinase-14 (MMP14), which was the first membrane type matrix metalloproteinase discovered, has been suggested to involve in many biological processes, such as invasion and basement membrane remodeling (Itoh and Seiki, 2006). Recent study showed that MMP2, MMP-14, MMP24, MMP25, and TIMP-3 could be candidates for molecular markers of gastric cancer compared with superficial gastritis (de la Pena et al., 2014). Similar to our results, we also found that the mRNA and protein level

Conflict of interest

None.

Acknowledgments

None.

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¹: Co-first authors.

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Increased expression of MMP14 correlates with the poor prognosis of Chinese patients with gastric cancer

Highlights

Abstract

Introduction

Section snippets

Sample collection

MMP14 is expressed at high levels in gastric cancer

High protein expression of MMP14 was associated with gastric cancer progression and poor prognosis

Discussion

Conflict of interest

Acknowledgments

Hum. Pathol.

Hum. Pathol.

Ann. Oncol.

Biochim. Biophys. Acta

Mod. Pathol.

J. Biol. Chem.

MicroRNA-133a regulates the mRNAs of two invadopodia-related proteins, FSCN1 and MMP14, in esophageal cancer

Br. J. Cancer

Global gene expression profiling of human pleural mesotheliomas: identification of matrix metalloproteinase 14 (MMP-14) as potential tumour target

PLoS One

Expression of the matrix metalloproteases 2, 14, 24, and 25 and tissue inhibitor 3 as potential molecular markers in advanced human gastric cancer

Dis. Markers

Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008

Int. J. Cancer