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Clinical impact of pentraxin family expression on prognosis of pancreatic carcinoma.

ABSTRACT: BACKGROUND: Inflammatory mediators may have decisive roles at different stages of tumour development. Mediators within the pentraxin family may be used as strong biomarkers in prognosis of advanced pancreatic carcinoma patients. METHODS: Using pancreatic carcinoma cell lines and gene transfectant, we measured long pentraxin (PTX3) level in culture solution and carried out cellular migration assay in vitro. In vivo study of the treatment-naive patients with advanced pancreatic carcinoma assigned to undergo gemcitabine therapy was prospectively conducted to measure and investigate the role of plasma PTX3, C-reactive protein (CRP), and eight inflammatory mediators by using collected clinical data. RESULTS: Elevated PTX3 production was observed in several cell lines, and a direct relationship between migratory activity and PTX3 level was identified in vitro. High PTX3 level (117 days) was significantly less than that of patients with low PTX3 level (357 days, P<0.001). Multivariate analysis of the pancreatic carcinoma revealed a strong correlation between pentraxin family member expression and prognosis of pancreatic carcinoma. The relationship between PTX3 expression and the expression of other pro-inflammatory mediators indicated that PTX3 level is positively correlated with levels of CRP, interleukin-6, and macrophage-inhibitory factor. CONCLUSION: Pentraxin family members, especially PTX3, may be used as promising biomarkers in the prognosis of pancreatic carcinoma patients.

SUBMITTER: Kondo S

PROVIDER: S-EPMC3738116 | biostudies-other | 2013 Aug

REPOSITORIES: biostudies-other

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Project description:IntroductionPancreatic ductal adenocarcinoma is associated to dismal prognosis despite the use of palliative chemotherapy, partly due to the lack of knowledge of biological processes underlying disease progression. Exosomes have been identified as biomarkers sources in different cancer types. Aim of the study was to analyse the contents of circulating exosomes in patients with pancreatic cancer who received palliative chemotherapy.Patients and methodsPatients were submitted to blood sample collection before chemotherapy (T0) and after 3 months (T3). We quantified by an ELISA-based technique specific proteins of cancer-derived exosomes (CD44,CD44v6,EpCAM,CD9,CD81,Tspan8,Integrin α6,Integrin β4,CD24,CXCR4). We correlated the baseline levels of these factors and changes between T3 and T0 and survival outcomes. Survival analyses were performed by Kaplan-Meier method. Correlation was assessed by log-rank test and level of statistical significance was set at 0.05. Multivariate analysis was performed by logistic regression analysis.ResultsNineteen patients were enrolled. EpCAM T0 levels and increased EpCAM levels from T0 to T3 were those mostly associated with differences in survival. Patients having higher EpCAM had median progression free survival (PFS) of 3.18vs7.31 months (HR:2.82,95%CI:1.03-7.73,p = 0.01). Overall survival (OS) was shorter for patients having higher EpCAM (5.83vs16.45 months,HR:6.16,95%CI:1.93-19.58,p = 0.0001) and also response rates (RR) were worse (20%vs87%,p = 0.015). EpCAM increase during treatment was associated with better median PFS (2.88vs7.31 months,HR:0.24,95%CI:0.04-1.22,p = 0.003). OS was also better (8.75vs11.04 months, HR:0.77,95%CI:0.21-2.73,p = 0.66) and RR were 60%vs20% (p = 0.28). Among clinical factors that might determine changes on PFS and OS, only ECOG PS was associated to significantly worse PFS and OS (p = 0.0137and<0.001 respectively).Multivariate analysis confirmed EpCAM T0 levels and EpCAM T0/T3 changes as independent prognostic factors for PFS.ConclusionsPancreatic cancer patients exosomes express EpCAM, whose levels change during treatment. This represents a useful prognostic factor and also suggests that future treatment modalities who target EpCAM should be tested in pancreatic cancer patients selected by exosome EpCAM expression.

Project description:Pancreatic metastases from renal cell carcinoma are uncommon and their prognostic significance is not well defined. In this analysis we evaluated the outcome of patients with pancreatic metastases treated with either targeted therapies or local treatment to the pancreas. Patients with pancreatic metastases from renal cell carcinoma treated between 1993 and 2014 were identified from 11 European centers. Clinical records were retrospectively reviewed. Kaplan-Meier method and log-rank test were used to evaluate progression-free survival and overall survival. Cox's proportional hazard models were used for survival analysis. In total, 276 PM patients were evaluated, including 77 (28%) patients treated by either surgery or radiotherapy to the pancreas, and 256 (93%) who received systemic therapy. Median time from nephrectomy to diagnosis of pancreatic metastases was 91 months (IQR 54-142). Disease control rate after first-line TTs was 84%, with a median progression-free survival of 12 months (95% CI 10-14). Median overall survival was 73 months (95% CI 61-86) with a 5-year OS of 58%. Median OS of patients treated with local treatment was 106 months (95% CI 78-204) with a 5-year overall survival of 75%. On multivariable analysis, nephrectomy (HR 5.31; 95%CI 2.36-11.92; p<0.0001), Memorial Sloan Kettering/International Metastatic RCC Database Consortium prognostic score (HR 1.45, 95% CI 0.94-2.23 for intermediate vs good vs risk; HR 2.76 95%, CI 1.43-5.35 for poor vs good risk p = 0.0099) and pancreatic local treatment (HR 0.48; 95%CI 0.30-0.78 p = 0.0029) were associated with overall survival. Difference in median OS between patients with PM and that reported in a matched-control group of mRCC patients with extrapancreatic metastases was statistically significant (p < .0001). Pancreatic metastases from renal cell carcinoma usually occur years after nephrectomy, are associated with an indolent behavior and a prolonged survival. Targeted therapies and locoregional approaches are active and achieve high disease control rate.

Project description:BackgroundPancreatic cancer is a common malignant tumor. Multiple studies have shown that procollagen lysyl-hydroxylase (PLOD) family genes were closely related to tumor progression and metastasis in a variety of human cancers. This study aimed to explore the prognosis and biological role of PLOD family genes in pancreatic adenocarcinoma (PAAD).MethodsGEPIA, GEO, HPA, CCLE, Kaplan-Meier plotter, cBioPortal, LinkedOmics, DAVID6.8, STRING, and TIMER were employed to determine the prognostic values and biological function of PLOD family members in PAAD.ResultsThe mRNA and protein expression patterns of PLOD family members were noticeably up-regulated in PAAD compared with normal tissues. PLOD family gene expression was also up-regulated in pancreatic cancer cell lines. PLOD1 was correlated with histological and pathological grades of pancreatic cancer. PLOD2 was related to histological grade. The high expression of PLOD1-2 was correlated with the poor overall survival rate and relapse-free survival rate in patients with PAAD. Additionally, PLODs showed high sensitivity and specificity in distinguishing pancreatic cancer from normal tissues. Through the functional enrichment analysis of PLOD-related genes in PAAD, we found that PLODs were enriched in collagen fiber tissue structure, lysine degradation, and collagen biosynthesis. Pathway analysis confirmed that PLODs regulated the proliferation, migration, and metastasis of pancreatic cancer through the RalGEF-Ral signaling pathway. Furthermore, the level of expression of PLOD1-2 was positively correlated with the activity of tumor-infiltrating immune cells, including CD8+T cells, neutrophils, macrophages, and dendritic cells. The level of expression of PLOD3 was inversely correlated with the level of infiltration of CD8+T cells. PLOD1 and PLOD2 were highly expressed in pancreatic cancer tissues with TP53 and KRAS mutations, respectively. However, the level of expression of PLOD3 in SMAD4 wild-type pancreatic cancer was increased.ConclusionThe findings showed that individual PLOD genes or PLOD family genes could be potential prognostic biomarkers for PAAD.

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Clinical impact of pentraxin family expression on prognosis of pancreatic carcinoma.

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