Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate of

Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate of 5%. metastasis (P=0.001). High serum levels of TGF-β1 were significantly correlated with reduced patient survival. Multivariate analysis revealed that TGF-β1 lymph node metastasis and tumor stage were independent factors for PDAC survival. Our results indicate that serum TGF-β1 may be used as a potential prognostic marker for PDAC. for 15 min. Serum samples were stored at -80°C until required for the assay. Detection of TGF-β1 expression in serum Quantitative enzyme-linked immunosorbent assay (ELISA) kits were used to assess R1626 the levels of human TGF-β1 according to the manufacturer’s instructions. A total of 200 μL of prediluted sera was added to micro-titer wells precoated with anti-human TGF-β1 R1626 polyclonal antibodies followed by a biotin-conjugated mouse anti-TGF-β1 antibodies and streptavidin-horseradish peroxidase. Color was developed using a tetramethyl benzidine-hydrogen dioxide mixture and terminated with sulfuric acid. The absorbance of each well was determined using a spectrophotometer. Statistical analysis Data are reported as means±SD. The associations between TGF-β1 level and clinicopathological variables were examined using the χ2 test. The association with survival was analyzed using Kaplan-Meier analysis and curves were compared using the log-rank test and Cox regression analysis to adjust for other prognostic indicators. The receiver operating characteristic (ROC) curve was determined and the area under the curve (AUC) was calculated as a comparative measure of diagnostic accuracy. Multivariate Cox regression analysis was used to analyze the relationship between independent and dependent variables. All statistical analyses were performed with the IBM SPSS Statistical software (SPSS Statistics 17.0 USA). Statistical significance was defined as Pbenign pancreas disease (non-lymph node metastasis (stage III+IV (C). Influence of TGF-β1 level on overall survival in PDAC Median survival from the time of PDAC operation for all patients was 18 months (range of R1626 0.6-26 months) with a 5-year overall survival of 18.7%. By univariate analysis the 5-year median overall survival was 21.7% in low TGF-β1 level groups which was significantly higher than the high TGF-β1 level groups (15.3%; P<0.01 Figure 2A). Figure 2 Kaplan Meier survival curve for low and high TGF-β1 Mmp2 levels in plasma of pancreatic ductal adenocarcinoma patients (A) for patients with stage I and II or stage III and IV (B) and for pancreatic cancer patients with lymph node metastasis and … Cox regression multivariate analysis indicated that only serum TGF-β1 level (P=0.001; HR=1.213 95 1.204 tumor stage of PDAC (P=0.012; HR=1.158 95 1.127 and lymph node metastasis (P=0.018; HR=1.214 95 1.374 were independent prognostic factors for patients with PDAC (Table 1). Kaplan-Meier R1626 survival curves for stage and lymph node metastasis of PDAC are shown in Figure 2 B and C). Discussion TGF-β1 is a pleiotropic cytokine that depending on the cell niche can display either anti-inflammatory or proinflammatory effects (17). A recent study has found that TGF-β1 could shape the metastatic niche and favor the maintenance of an immunosuppressive phenotype in mesenchymal cells (18 -20). TGF-β has a dual role in tumor development including tumor suppression through inhibition of proliferation and induction of apoptosis in multiple cell types or promotion of tumor cell invasiveness and metastasis through modulation of the immune system as well as of the tumor microenvironment (21). Many studies have found that TGF-β1 is activated and released into the blood under ischemia and hypoxia stress and it is markedly induced and rapidly activated in R1626 the infarcted myocardium. Bioactive TGF-β1 is released in the cardiac extracellular fluids 3-5 h following reperfused infarction (22). Tissue and serum TGF-β1 were also significantly increased in patients with cancers indicating its predictive and prognostic roles in patients with this disease. In our study serum levels of TGF-β1 were found to be significantly higher in PDAC patients than in normal controls or patients with benign pancreas disease. Furthermore the serum TGF-β1 level increased R1626 with increased tumor stage lymph node metastasis and distant metastasis. These.