Abstract
BackgroundThe aim of the present study was to investigate the association between serum levels of matrix metalloproteinase 11 (MMP-11) and responses to front-line chemotherapy and prognosis in advanced unresectable gastric adenocarcinoma.MethodsClinical data concerning 86 patients with advanced gastric adenocarcinoma (stages III c to IV), treated in Beijing Chao-Yang Hospital from 2005 to 2009, were reviewed retrospectively. Adenocarcinoma was confirmed by pathology and patients received 5-fluorouracil-based front-line combination chemotherapy with third generation chemotherapeutic agents including paclitaxel, docetaxel and oxaliplatin. The regimen was repeated every two to three weeks, and the first evaluation was carried out after three cycles. The median cycle of chemotherapy was 6 (ranging from three to twelve cycles). Serum MMP-11 protein from the 86 patients was examined using enzyme-linked-immunosorbent-assay (ELISA) prior to chemotherapy and after three cycles of chemotherapy. Serum samples from healthy individuals were used as controls.ResultsThe response rate (RR, complete response plus partial response) to chemotherapy in the 86 patients was 44.2% (38/86). The median TTP (time to progression) and overall survival (OS) in patients who responded to chemotherapy were 6.0 and 10.0 months, respectively. The response rate to chemotherapy in patients with high levels of serum MMP-11 (42.9%; 9/21) was similar to that in patients with low levels (44.6%; 29/65) (P = 0.935). Patients with low serum levels of MMP-11 had a higher median survival time and 1-year survival rate than those with high levels (11 months vs. 8 months, 50.2% vs. 21.7%, P = 0.017), although the TTP was comparable in all patients, irrespective of serum MMP-11 level (P = 0.178). Serum MMP-11 levels were correlated with lymph node metastasis (P = 0.006). Cox multivariate regression analysis demonstrated that the serum level of MMP-11 was an independent prognostic factor for patients presenting with advanced gastric carcinoma.ConclusionsSerum levels of MMP-11 in Chinese patients with advanced gastric carcinoma were not associated with the response to front-line chemotherapy, but could play an important role in lymph node metastasis and prognosis.
Highlights
The aim of the present study was to investigate the association between serum levels of matrix metalloproteinase 11 (MMP-11) and responses to front-line chemotherapy and prognosis in advanced unresectable gastric adenocarcinoma
Matrix metalloproteinases (MMPs)-11 differs from other MMPs, which are expressed as proenzymes and processed to active forms through proteolytic cleavage activated extracellularly, indicating that MMP11 could have a unique role in tumor development and progression [6]
Histological differentiation determined that 54 patients (62.8%) had intestinal type adenocarcinoma, 20 (23.2%) had mucinous carcinoma and signet-ring cell carcinoma was present in 12 patients (14.0%)
Summary
The aim of the present study was to investigate the association between serum levels of matrix metalloproteinase 11 (MMP-11) and responses to front-line chemotherapy and prognosis in advanced unresectable gastric adenocarcinoma. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that mediate degradation of components of the extracellular matrix [2]. They are predominantly produced by stromal cells in response to the presence of tumor cells [3]. MMP-11 differs from other MMPs, which are expressed as proenzymes and processed to active forms through proteolytic cleavage activated extracellularly, indicating that MMP11 could have a unique role in tumor development and progression [6]. Clinicopathological studies have demonstrated that MMP-11 is an important factor in tumor progression in various malignant tumors including pulmonary cancer [7], head and neck carcinoma [8,9] and breast carcinoma [10]
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