Dataset Information

Clinical Significance of Serum NEDD9 Levels in Patients with Pancreatic Cancer.

ABSTRACT: INTRODUCTION:Pancreatic cancer (PC) is a lethal malignancy. Various diagnostic, predictive, and prognostic biomarkers have been evaluated. This study was conducted to investigate the serum levels of neural precursor cell expressed developmentally downregulated protein 9 (NEDD9) in patients with PC and the relationship between tumor progression and known prognostic parameters. MATERIALS AND METHODS:Serum samples were obtained on first admission before any treatment. Serum NEDD9 levels were determined using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched healthy controls were included in the analysis. RESULTS:In a three year period, 32 patients with a pathologically-confirmed diagnosis of PC were enrolled in this study. The median age at diagnosis was 61 years, range 38 to 84 years; the majority of the patients in the group were men (n = 20, 62.5%). The tumor was located in the head of pancreas in 21 (65.6%) patients. Forty-one percent of 17 metastatic patients who received palliative CTx (chemotherapy) were CTx-responsive. The baseline serum NEDD9 levels were significantly higher in patients with PA than in the control group (p = 0.03). Median OS of the whole group were 27 ± 7.3 weeks. Alcohol intake, performance status, and LDH levels were found to be significant prognostic factors (p = 0.006, p < 0.001, and p < 0.001, respectively). However, serum NEDD9 levels had no significantly effect on progression free survival (PFS) and overall survival (OS) (p = 0.71 and p = 0.58, respectively). CONCLUSIONS:NEDD9 is identified as a secretory biomarker for PC but it has no prognostic role.

SUBMITTER: Afsar CU

PROVIDER: S-EPMC6316687 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Clinical Significance of Serum NEDD9 Levels in Patients with Pancreatic Cancer.

Afsar Cigdem Usul CU Karabulut Mehmet M Karabulut Senem S Ozal Safiye Tokgoz ST Cikot Murat M Serilmez Murat M Tas Faruk F

Biomolecules 20181210 4

<h4>Introduction</h4>Pancreatic cancer (PC) is a lethal malignancy. Various diagnostic, predictive, and prognostic biomarkers have been evaluated. This study was conducted to investigate the serum levels of neural precursor cell expressed developmentally downregulated protein 9 (NEDD9) in patients with PC and the relationship between tumor progression and known prognostic parameters.<h4>Materials and methods</h4>Serum samples were obtained on first admission before any treatment. Serum NEDD9 lev ...[more]

PMID: 30544746

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Project description:BackgroundInteractions between the programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) lead to immune evasion in various tumors and are associated with poor prognosis in patients with pancreatic cancer; however, the roles of PD-L1-containing exosomes in pancreatic cancer is poorly understood. Here, we investigated the correlation between circulating exosomal PD-L1 (exoPD-L1) and PD-L1 expression in tumor tissue, and survival outcomes in patients with advanced PDAC.MethodsExosomes were derived from pre-treatment serum samples isolated using ExoQuick kit from 77 patients with advanced pancreatic cancer. Exosomal PD-L1 (exoPD-L1) was detected by enzyme-linked immunosorbent assay, and matched tumor tissues PD-L1 expression were evaluated by PD-L1 immunohistochemistry (22C3) assay, described with combined positive score. Cutoff value of exoPD-L1 for survival was assessed with receiver operating characteristic curve analysis. Kaplan-Meier analysis was performed to obtain median overall survival (OS), and hazard ratio was estimated using a stratified Cox regression model.ResultsThe median exoPD-L1 serum concentration was 0.16 pg/mg, with undetected levels in seven patients. ExoPD-L1 levels were significantly higher in patients with systemic disease than in those with locally advanced disease (p = 0.023). There was a significantly higher proportion of elevated exoPD-L1 levels in patients with positive PD-L1 expression compared to patients with negative PD-L1 expression (p = 0.001). Patients were classified into groups with low and high exoPD-L1 levels using ROC curve-derived cutoffs (0.165 pg/mg; area under the curve, 0.617; p = 0.078). At a median follow-up of 8.39 months, the median OS was 13.2 (95% CI, 8.17-18.3) and 6.36 months (95% CI, 3.27-9.45) in the low and high exoPD-L1 groups, respectively (HR = 0.61; 95% CI, 0.35-1.04; p = 0.059). ExoPD-L1 levels did not affect the proportion of CD8+CD69+ effector cytotoxic T cells in either of the groups (p = 0.166).ConclusionsThe serum-derived exoPD-L1 levels were higher in metastatic pancreatic cancer than locally advanced disease. Collectively, higher serum exoPD-L1 levels in patients with advanced pancreatic cancer suggested worse survival outcomes and may have clinical implications.

Project description:BackgroundCD40-CD40 ligand (CD40L) interaction is considered to contribute to the promotion of prothrombotic responses and production of angiogenesis-associated factor in addition to adaptive immune responses. Recently, the role of soluble CD40L (sCD40L) has gained interest in cancer, although its exact functions remain unknown. This study evaluated the clinical significance of sCD40L in patients with pancreatic ductal adenocarcinoma (PDAC) and validated its utility as a PDAC diagnostic and prognostic biomarker.MethodsSerum sCD40L levels were measured by chemiluminescent immunoassay and compared among normal, chronic pancreatitis (CP, high-risk), and PDAC group in both training (n=25 per group) and independent validation (n=30, 30, and 55, respectively) datasets through one-way ANOVA test with the post-hoc Bonferroni method. To evaluate the diagnostic potential of serum sCD40L for PDAC, receiver operating characteristic (ROC) curves were generated and logistic regression analysis was conducted. To investigate the sCD40L-assoicated cytokines/chemokines in PDAC, cytokines/chemokines levels were analyzed by a MILLIPLEX MAP Human Cytokine/Chemokine Kit. To assess the prognostic potentials of sCD40L, Kaplan-Meier survival curve and Cox proportional-hazards regression analysis were applied.ResultsSerum sCD40L levels were significantly higher in PDAC group compared with non-cancer groups in both training (p<0.05) and validation (p<0.05) datasets. Clinically, serum sCD40L closely correlated with unresectability (?s=0.342, p=0.011) and distant metastasis (?s=0.294, p=0.030) of PDAC. ROC curve and logistic regression analysis demonstrated the remarkable predictive potentials of serum sCD40L for PDAC (80.0% sensitivity and 85.5% specificity at cut-off point, 0.45; logistic regression), superior to those of CA19-9 and CEA. According to cytokines/chemokines assay, serum sCD40L levels were closely correlated with serum levels of pro-angiogenic cytokines (EGF, VEGF, IL-8) and immunosuppressive cytokines (IL-6, IL-10, IL-1RA). Kaplan-Meier survival analysis demonstrated patients with high-serum sCD40L (>35,000 ng/ml) had a poorer prognosis than those with low-serum sCD40L (log-rank, p=0.015). Multivariate Cox regression analysis yielded a hazard ratio of 2.509 (95% CI, 1.038-6.067, p=0.041) for mortality in the high-serum sCD40L group.ConclusionsSerum sCD40L is correlated with immunosuppression and angiogenesis in PDAC carcinogenesis/progression, and is a promising diagnostic and prognostic biomarker for PDAC superior to CA19-9 and CEA.

Dataset Information

Clinical Significance of Serum NEDD9 Levels in Patients with Pancreatic Cancer.

Publications

Clinical Significance of Serum NEDD9 Levels in Patients with Pancreatic Cancer.

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