This study demonstrated that MMP-11 over-expression was consistently detected in advanced gastric adenocarcinoma. MMP-11 serum levels in 86 cases of advanced gastric adenocarcinoma were not associated with responses to 5-fluorouracil-containing chemotherapy and TTP as front-line chemotherapy. However, they correlated with lymph node status and mOS. These data suggest that MMP-11 could be involved in metastatic dissemination and be regarded as an independent prognostic factor of advanced gastric adenocarcinoma.
Despite improvements in surgical techniques and the development of new chemotherapy regimes, gastric carcinoma remains the third leading cause of cancer-related deaths in China [
14]. Previously, we demonstrated that MMP-11 was a cancer-related protein and its over-expression was consistently confirmed at mRNA and protein levels in primary gastric adenocarcinoma tumors compared with matched normal tissues. Currently, the impact of MMP-11 on advanced gastric adenocarcinoma is uncertain. The aim of the study was to evaluate the associations between the expression of MMP-11 protein in serum and response to front-line chemotherapy and prognosis in advanced gastric adenocarcinoma. The results demonstrate that serum MMP-11 levels are not correlated with response to front-line chemotherapy, but are correlated with lymph node status and mOS in patients with advanced gastric adenocarcinoma.
MMPs have a broad spectrum of proteolytic activities towards extracellular matrix (ECM) components, and are believed to be involved in several biological processes including embryo implantation and morphogenesis, cell migration, metastasis, tumor invasion and wound healing [
15,
16]. MMP-11 over-expression has been demonstrated in human cancers including oral cancer [
17,
18], desmoid tumors [
19], non-small cell lung cancer [
20] and esophageal adenocarcinoma [
21]. Furthermore, increased MMP-11 gene expression is correlated with increased aggressiveness of tumors and a poor clinical outcome [
22,
23]. Clinical trials have demonstrated that a high level of MMP-11 expression is correlated with a lower survival rate among patients with breast, non-small cell lung cancer and colon cancer [
24,
25]. Deng et al [
6] reported that the BGC823 cell-line silenced MMP-11 expression and significantly inhibited cell proliferation and colony formation in soft agar medium and tumorigenicity in nude mice. The same authors also demonstrated that MMP-11 promoted the proliferation, invasion and tumorigenicity of the AGS cell line. Such experimental evidence has provided a causative role for MMP-11 protein during tumor progression. This study is the first to identify a correlation between MMP-11 expression and outcome in advanced gastric adenocarcinoma patients. In this study, MMP-11 protein levels appeared to correlate with invasion potential and high levels were related to the extent of lymph node metastasis in GC (P = 0.006), similar to data reported for other malignancies [
26]. Moreover, this study demonstrates that patients with high level MMP-11 expression had a shorter survival time than patients with low levels of MMP-11. In other words, the findings indicate that MMP-11 protein is an independent prognostic factor for patients with advanced gastric adenocarcinoma. As has been reported previously in breast and head and neck cancer, there were no obvious associations among the degree of tumor differentiation, MMP-11 protein level, sex and age.
There was no statistical difference between MMP-11 levels with mTTP and chemotherapy response. Potential reasons for this could be: (1) there were no differences in terms of the effects of MMP-11 on mTTP and chemotherapy response in advanced gastric adenocarcinoma; (2) the number of cases studied in the current research was not large enough. The OS in the present study was different from the results reported for the V325 trial [
27]. Possible explanations include the fact that this was a retrospective study; several factors could influence survival. The chemotherapy regimens used in the present study differed in some ways from that used in the V325 trial, which could affect OS.