Prognostic value of matrix metalloproteinase-9 in gastric cancer: a meta-analysis.

BACKGROUND/AIMS: The purpose of this study was to evaluate the effect of matrix metalloproteinase-9 overexpression on clinical outcome of gastric cancer using a meta-analysis. METHODOLOGY: Relevant studies concerning the association between Matrix metalloproteinase-9 expression and survival of patients with gastric cancer were collected from electronic databases. Hazard ratios (HRs) with 95% confidence intervals (Cls) were calculated to estimate the association. Subgroup analysis was calculated to evaluate potential sources of heterogeneity. Besides, we also assessed the relationship between Matrix metalloproteinase-9 level and relevant clinicopathological parameters by estimating the Odds ratios (ORs) with 95% Cls. RESULTS: Ten studies with 1,478 patients were included to perform a meta-analysis of the survival results. Pooled HRs indicated that MMP-9 overexpression had a negative impact on the over survival (OS) of patients with gastric cancer (HR = 1.69, 95% Cl: 1.29-2.23, P = 0.00), without significant heterogeneity (chi2 = 14.17, I2 = 36.5%, P = 0.117). Similarly, high level of MMP-9 tended to be correlated with lymph node metastasis (OR = 1.91, 95% Cl: 1.40-2.59, P < 0.05) and presence of vascular invasion (OR = 2.64, 95% CI: 1.52-4.59, P <0.05). CONCLUSIONS: This meta-analysis shows that Matrix metalloproteinase-9 overexpression is a poor prognostic factor in patients with gastric cancer. However, larger scale and randomized studies are needed to confirm its potential clinical value.

[Analysis of pancreatic cancer peripheral blood by comparative proteomics].

OBJECTIVE: To identify protein markers for the early diagnosis of pancreatic cancer by a comparative proteomic method. METHODS: Comparative analysis on the pancreatic peripheral blood protein profiling from 20 pancreatic cancer patients, 10 chronic pancreatitis patients and 20 cancer-free controls from May 2007 to September 2008 was carried out by two-dimensional fluorescence electrophoresis (2D-DIGE). Differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The significance difference proteins were confirmed by Western-blot. RESULTS: A differentially expressed proteins: complement 3 (C3) was identified. The gray level of C3 in pancreatic cancer tissue, chronic pancreatitis, and normal control group were 1.63 ± 0.28, 0.65 ± 0.13 (t = 11.81, P = 0.00) and 0.88 ± 0.19 (t = 9.93, P = 0.00), respectively. C3 was high expression in pancreatic cancer group compared with normal control group. The expression of C3 was higher in pancreatic cancer group than in chronic pancreatitis group. The high expression of C3 in pancreatic carcinoma was confirmed by Western blot. CONCLUSIONS: 2D-DIGE and MALDI-TOF-MS technology is a quick, easy and practical method to screen for specific biomarkers in serum of patients with pancreatic carcinoma. The identified protein C3 in this study may be as specific serum biomarkers of pancreatic carcinoma.

Expression and clinical significance of apolipoprotein E in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a poor prognosis. Our previous proteomic analysis found apolipoprotein E (ApoE) protein to be up-regulated in the sera of patients with PDAC. In this study, we sought to confirm this finding and investigate the relationship between ApoE and PDAC. We measured ApoE expression in tissues from PDAC patients and normal controls (NC) by real-time PCR, western blot, and immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was applied to measure the levels of ApoE and carbohydrate antigen 19-9 (CA19-9) in the sera from patients with PDAC and NC. Real-time PCR and western blots showed that the ApoE mRNA and protein levels were up-regulated in PDAC tissues. The immunohistochemical results revealed that overexpression of ApoE was detected in 43 of 55 (78.2 %) PDAC cases and 3 of 20 (15 %) NC. High levels of ApoE were more likely in PDAC patients with advanced T status and TNM stages (p = 0.023 and p = 0.018, respectively). The ELISA results also confirmed that ApoE levels were elevated in the sera of PDAC patients. The sensitivity and specificity for distinguishing PDAC from NC were 76.2 and 71.4 %, respectively, for ApoE, 66.7 and 85.7 %, respectively, for CA19-9, and 81.0 and 85.7 %, respectively, for their combination. These results suggest that ApoE may be a potential PDAC-related biomarker and alone or in combination with other markers may provide additional information for the diagnosis and clinical management of PDAC.

Identification and verification of transthyretin as a potential biomarker for pancreatic ductal adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide and is difficult to detect at its early stages when treatment is most effective. Therefore, we performed a comparative proteomic study to identify new biomarkers for the detection of PDAC. METHODS: Serum samples from patients with PDAC, chronic pancreatitis and normal controls were compared using two-dimensional difference gel electrophoresis (2D-DIGE). Differentially expressed separated proteins were subsequently identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Then, transthyretin (TTR), one of the differentially expressed proteins, was validated through real-time PCR, western blot and immunohistochemistry. Finally, enzyme-linked immunosorbent assays (ELISA) were employed to confirm the levels of transthyretin in the sera. RESULTS: A total of 21 protein spots showed greater than 1.5-fold changes in expression level in the sera from PDAC patients compared with the normal controls. Among the identified proteins, validation experiments verified the differential expression of transthyretin in PDAC tissue, confirming the proteomic data showing that transthyretin was significantly elevated in patients with PDAC. The ELISA results revealed that the sensitivity and specificity for TTR and CA19-9 in distinguishing PDAC patients from normal individuals were 90.5, 47.6, 66.7 and 85.7 %, respectively, and 81.0 and 85.7 % for their combination. CONCLUSIONS: These results suggest that the level of transthyretin is elevated in patients with PDAC. In combination with CA19-9, transthyretin may provide additional information for the detection of PDAC and should be further investigated.