Dataset Information

High Expression of Cancer-Derived Glycosylated Immunoglobulin G Predicts Poor Prognosis in Pancreatic Ductal Adenocarcinoma.

ABSTRACT: Background: Cancer-derived immunoglobulin G (CIgG) has been detected in various cancers and plays important roles in carcinogenesis. The present study aimed to investigate its clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: Using tissue microarrays (TMAs) and immunohistochemistry, we assessed CIgG expression in 326 patients who underwent surgical resection for PDAC. The associations between CIgG expression and clinicopathological features and clinical outcomes were analyzed. Functional experiments were also performed to investigate the effect of CIgG on PDAC cells. Results: High CIgG expression was related to poor tumor differentiation and metastasis during follow-up and was associated with poor disease-free survival (DFS) and overall survival (OS). A multivariate Cox regression analysis identified high CIgG expression as an independent prognostic factor for DFS and OS. The incorporation of CIgG expression improved the accuracy of an established prognosis prediction model for 1-year OS and 2-year OS. In vitro studies showed that knocking down CIgG profoundly suppressed the proliferation, migration, and invasion capacity of PDAC cells. Conclusions: CIgG contributes to the malignant behaviors of PDAC and offers a powerful prognostic predictor for these patients.

SUBMITTER: Cui M

PROVIDER: S-EPMC7052941 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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High Expression of Cancer-Derived Glycosylated Immunoglobulin G Predicts Poor Prognosis in Pancreatic Ductal Adenocarcinoma.

Cui Ming M You Lei L Zheng Bang B Huang Xinmei X Liu Qiaofei Q Huang Jing J Pan Boju B Qiu Xiaoyan X Liao Quan Q Zhao Yupei Y

Journal of Cancer 20200203 8

<b>Background</b>: Cancer-derived immunoglobulin G (CIgG) has been detected in various cancers and plays important roles in carcinogenesis. The present study aimed to investigate its clinical significance in pancreatic ductal adenocarcinoma (PDAC). <b>Methods</b>: Using tissue microarrays (TMAs) and immunohistochemistry, we assessed CIgG expression in 326 patients who underwent surgical resection for PDAC. The associations between CIgG expression and clinicopathological features and clinical out ...[more]

PMID: 32127948

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Project description:BackgroundEpidermal growth factor receptor (EGFR) is highly expressed in pancreatic ductal adenocarcinoma (PDAC) and is involved in tumorigenesis and development. However, EGFR expression alone has limited clinical and prognostic significance. Recently, the cross-talk between EGFR and G-protein-coupled chemokine receptor CXCR4 has become increasingly recognized.MethodsIn the present study, immunohistochemical staining of EGFR and CXCR4 was performed on paraffin-embedded specimens from 131 patients with surgically resected PDAC. Subsequently, the associations between EGFR expression, CXCR4 expression, EGFR/CXCR4 coexpression and clinicopathologic factors were assessed, and survival analyses were performed.ResultsIn total, 64 (48.9%) patients expressed EGFR, 68 (51.9%) expressed CXCR4, and 33 (25.2%) coexpressed EGFR and CXCR4. No significant association between EGFR and CXCR4 expression was observed (P = 0.938). EGFR expression significantly correlated with tumor differentiation (P = 0.031), whereas CXCR4 expression significantly correlated with lymph node metastasis (P = 0.001). EGFR/CXCR4 coexpression was significantly associated with lymph node metastasis (P = 0.026), TNM stage (P = 0.048), and poor tumor differentiation (P = 0.004). By univariate survival analysis, both CXCR4 expression and EGFR/CXCR4 coexpression were significant prognostic factors for poor disease-free survival (DFS) and overall survival (OS). Moreover, EGFR/CXCR4 coexpression significantly increased the hazard ratio for both recurrence and death compared with EGFR or CXCR4 protein expression alone. Multivariate survival analysis demonstrated that EGFR/CXCR4 coexpression was an independent prognostic factor for DFS (HR = 2.33, P<0.001) and OS (HR = 2.48, P = 0.001).ConclusionsIn conclusion, our data indicate that although EGFR expression alone has limited clinical and prognostic significance, EGFR/CXCR4 coexpression identified a subset of PDAC patients with more aggressive tumor characteristics and a significantly worse prognosis. Our results suggest a potentially important "cross-talk" between CXCR4 and EGFR intracellular pathways and indicate that the simultaneous inhibition of these pathways might be an attractive therapeutic strategy for PDAC.

Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and is not a clinically homogeneous disease, but subsets of patients with distinct prognosis and response to therapy can be identified by genome-wide analyses. Mutations in major PDAC driver genes were associated with poor survival. By bioinformatics analysis, we identified protocadherins among the most frequently mutated genes in PDAC suggesting an important role of these genes in the biology of this tumor. Promoter methylation of protocadherins has been suggested as a prognostic marker in different tumors, but in PDAC this epigenetic modification has not been extensively studied. Thus, we evaluated whether promoter methylation of three frequently mutated protocadherins, PCDHAC2, PCDHGC5 and PCDH10 could be used as survival predictors in PDAC patients.MethodsDNA extracted from 23 PDACs and adjacent non-neoplastic pancreatic tissues were bisulfite treated. Combined Bisulfite Restriction Analysis (COBRA) coupled to denaturing high-performance liquid chromatography (dHPLC) detection and bisulfite genomic sequencing (BGS) were used to determine the presence of methylated CpG dinucleotides in the promoter amplicons analyzed.ResultsIn an exploratory analysis, two protocadherins showed the same pattern of CpG methylation in PDAC and adjacent non-neoplastic pancreatic tissues: lack of methylation for PCDHAC2, complete methylation for PCDHGC5. Conversely, the third protocadherin analyzed, PCDH10, showed a variable degree of CpG methylation in PDAC and absence of methylation in adjacent non-neoplastic pancreatic tissues. At Kaplan-Meier analysis, high levels of PCDH10 methylation defined according to the receiver operating characteristic (ROC) curve analysis were significantly associated with worse progression-free survival (PFS) rates (P = 0.008), but not with overall survival (OS). High levels of PCDH10 methylation were a prognostic factor influencing PFS (HR = 4.0: 95% CI, 1.3-12.3; P = 0.016), but not the OS.ConclusionsIn this study, we show for the first time that the methylation status of PCDH10 can predict prognosis in PDAC patients with a significant impact on the outcome in terms of progression-free survival. High levels of PCDH10 promoter methylation could be useful to identify patients at high risk of disease progression, contributing to a more accurate stratification of PDAC patients for personalized clinical management.

Project description:BackgroundHypoxia-inducible factor 1-alpha (HIF-1α) is overexpressed in pancreatic ductal adenocarcinomas (PDACs). However, the prognosis of high expression of HIF-1α in PDACs remains controversial because of lacking a solid support. A meta-analysis may help for a better understanding of the role of HIF-1α in the prognosis of PDACs.MethodsBy using a systematic approach, we conducted a meta-analysis from current literature. We performed an advanced search in PubMed, Embase, Cochrane Library and Web of Science databases. Recorded studies were published between September 1, 2001, and February 26, 2021, in English and related to the expression of HIF-1α in PDAC. We pooled and combined hazard ratios (HRs) and 95% confidence intervals (CIs) to show the effect of HIF-1α expression on overall survival (OS). We pooled also risk ratios (RRs) and 95% CIs to assess the correlation between HIF-1α expression and clinicopathological characteristics in PDAC. We evaluated publication bias among included studies through the Begg's test and Egger's test. From "Expression Plots" modules in the Gene Expression Profiling Interactive Analysis (GEPIA) database, we showed the difference of mRNA level for HIF1A between 179 pancreatic adenocarcinomas (PAADs) and 171 normal pancreatic tissues.ResultsThis meta-analysis included 11 studies and 764 patients. High expression of HIF-1α was associated with shorter OS compared to low HIF-1α expression in PDAC (HR =1.74, 95% CI: 1.49-2.04, P<0.001). Patients with high expression of HIF-1α tended to have an increased risk of earlier lymph node metastasis (LNM) (RR =1.63, 95% CI: 1.36-1.95, P<0.001), and more advanced clinical stage (RR =1.64, 95% CI: 1.38-1.97, P<0.001) compared to those with low HIF-1α expression. Expression plots from GEPIA database showed HIF1A overexpressed in PDAC tissues compared to normal tissues (Log2FC =2, P<0.01).ConclusionsHigh HIF-1α expression associated with worse prognosis of PDACs compared to low HIF-1α expression. Since HIF-1α expression is greater in PDAC than normal pancreas, it could serve as a prognostic factor and potential therapeutic target. However, due to the complex role of HIF-1α in physiology and pathology, therapeutic intervention should be considered with caution.

Dataset Information

High Expression of Cancer-Derived Glycosylated Immunoglobulin G Predicts Poor Prognosis in Pancreatic Ductal Adenocarcinoma.

Publications

High Expression of Cancer-Derived Glycosylated Immunoglobulin G Predicts Poor Prognosis in Pancreatic Ductal Adenocarcinoma.

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