Dataset Information

CXCR4--A Prognostic and Clinicopathological Biomarker for Pancreatic Ductal Adenocarcinoma: A Meta-Analysis.

ABSTRACT: Adenocarcinomas of the pancreatic duct (PDAC) are characteristically aggressive tumors that are extremely challenging to treat as curative surgical resection, the definitive treatment, is seldom possible. Regretably, most patients are diagnosed with metastatic disease at the time of initial presentation. In addition, current chemotherapeutic concepts that are used for advanced disease stages show frustrating results. Thus, there is an urgent need to identify novel therapeutic molecular targets that are associated with PDAC disease. Recently, the chemokine receptor CXCR4 has been demonstrated to be highly expressed in metastatic PDAC. However, the results of the published data on CXCR4 and its association with clinicopathological variables and prognosis in PDAC seem to be heterogeneous. Consequently, to clarify the relevance of CXCR4 as a biomarker in PDAC we performed a comprehensive literature search by using PubMed and Web of Science databases to identify articles that focused on the expression of CXCR4 in PDAC by using immunohistochemistry. Subsequently, data from nine relevant studies, encompassing 1183 patients were extracted, qualitatively assessed, and entered into a meta-analysis. By using a random effects model, the pooled hazard ratio of the seven studies that reported on patients overall survival revealed a correlation between expression of CXCR4 and poor prognosis (HR 1.49; 95% CI: 1.04-2.14; P = 0.03; I2 = 74%). Although heterogeneity became evident, subgroup analyses confirmed the prognostic value of CXCR4 in PDAC, especially in high-quality studies that performed multivariate analysis. In addition, meta-analysis revealed a strong association of CXCR4 expression with the UICC stage (OR: 3.40; 95% CI: 1.67-6.92; P = 0.0007; I2 = 0%) and metastatic disease (N-status: OR: 2.55; 95% CI: 1.56-4.15; P = 0.0002; I2 = 26%; recurrence to the liver: OR: 2.80; 95% CI: 1.48-5.29; P = 0.001; I2 = 0%). Taken together, our meta-analysis suggests that CXCR4 represents a useful prognostic biomarker in PDAC and might therefore be evaluated as a potential therapeutic target in the treatment of metastatic cancer disease of the pancreas.

SUBMITTER: Krieg A

PROVIDER: S-EPMC4474597 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) is fatal cancer that causes death. Early metastasis, resistance to chemotherapy, and lack of treatment contribute to a poor prognosis. Therefore, finding new therapeutic targets and biomarkers is a particularly urgent need to improve the survival of PDAC patients. Oligoadenylate synthetases-like (OASL), an antiviral enzyme produced by interferon (IFN), has been found to be associated with the occurrence and development of multiple cancers. However, its role in PDAC has been less well-studied. The value of OASL in PDAC was evaluated by bioinformatics and in vitro experiments.MethodsThe expression of OASL was evaluated using the Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) online websites. The survival time was also calculated by GEPIA. The correlation between OASL messenger RNA (mRNA) expression and immune infiltration was analyzed by the Tumor Immune Estimation Resource (TIMER) database. Clinical characteristics were revealed by The Cancer Genome Atlas (TCGA) data. A nomogram and forest plot were constructed based on univariate and multivariate Cox regression. Cell experiments [western blot assays, 3-(4,5-dimethylathiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, transwell assays, flow cytometry assays] were used to verify the value of OASL in PDAC cells (Panc-1, Mia paca-2, and Aspc-1).ResultsA higher expression of OASL was observed in PDAC (P<0.05). Patients with increased expression of OASL had worse overall survival (OS; P<0.05) and disease-specific survival (DSS; P<0.05). The expression of OASL was correlated with T stage (P=0.030) and N stage (P=0.004), radiation therapy (P=0.013), primary therapy outcome (P<0.001), residual tumor (P=0.028), and tumor location (P=0.004) by univariate analysis, which also confirmed that OASL was an independent prognostic factor. Moreover, OASL expression was positively associated with neutrophils. In vitro experiments indicated that knockdown of OASL inhibited cell viability and invasion while increasing apoptosis rate.ConclusionsHigh expression of OASL is associated with poor prognosis. Targeting OASL delays PDAC tumor progression in vitro. We highlight that OASL is a novel prognostic biomarker and therapeutic target of PDAC.

Dataset Information

CXCR4--A Prognostic and Clinicopathological Biomarker for Pancreatic Ductal Adenocarcinoma: A Meta-Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets