scholarly journals Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jun-Qi Liu ◽  
Xi-Wen Liao ◽  
Xiang-Kun Wang ◽  
Cheng-Kun Yang ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Characteristics ◽  
Prognostic Significance ◽  
Gene Set Enrichment Analysis ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Joint Effects ◽  
Prognosis Prediction ◽  
Genome Wide ◽  
The Relationship

Abstract Background This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Methods A total of 112 PDAC patients from TCGA and 48 patients from GEO were included in the analysis. The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) was carried out to identify potential mechanisms of these genes affecting prognosis. Results In TCGA database, high expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total scores calculated. Genome-wide co-expression and GSEA analysis suggested that the GPC2 may affect prognosis through sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway. Conclusion GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.

scholarly journals Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms

2020 ◽  
Author(s):  
Jun-qi Liu ◽  
Xi-wen Liao ◽  
Xiang-kun Wang ◽  
Cheng-kun Yang ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Characteristics ◽  
Prognostic Significance ◽  
Gene Set Enrichment Analysis ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Joint Effects ◽  
Prognosis Prediction ◽  
Genome Wide ◽  
The Relationship

Abstract Background: This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).Methods: A total of 112 PDAC patients from TCGA and 48 patients from GEO were included in the analysis. The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) was carried out to identify potential mechanisms of these genes affecting prognosis.Results: In TCGA database, high expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total scores calculated. Genome-wide co-expression and GSEA analysis suggested that the GPC2 may affect prognosis through sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway.Conclusion: GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.

scholarly journals Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms

2020 ◽  
Author(s):  
Jun-qi Liu ◽  
Xi-wen Liao ◽  
Xiang-kun Wang ◽  
Cheng-kun Yang ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Characteristics ◽  
Prognostic Significance ◽  
Gene Set Enrichment Analysis ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Joint Effects ◽  
Prognosis Prediction ◽  
Genome Wide ◽  
The Relationship

Abstract Background: This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Methods: A total of 112 PDAC patients from TCGA and 48 patients from GEO were included in the analysis. The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) was carried out to identify potential mechanisms of these genes affecting prognosis. Results: In TCGA database, high expression of GPC2 , GPC3 , and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total scores calculated. Genome-wide co-expression and GSEA analysis suggested that the GPC2 may affect prognosis through sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway. Conclusion: GPC2 , GPC3 , and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.

scholarly journals Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms

2020 ◽  
Author(s):  
Jun-qi Liu ◽  
Xi-wen Liao ◽  
Xiang-kun Wang ◽  
Cheng-kun Yang ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Characteristics ◽  
Prognostic Significance ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Joint Effects ◽  
Prognosis Prediction ◽  
Genome Wide

Abstract Background: This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA).Methods: A total of 112 PDAC patients from TCGA were included in the analysis.The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) to identify potential underlying mechanisms.Results: High expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total score calculated. Genome-wide co-expression and GSEA analyses suggested that the GPC2 mechanisms affecting prognosis involved sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway.Conclusion: GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and the combination of these genes showed a higher efficiency for prognosis prediction.

scholarly journals Immunohistochemical expression of NEDD9, E-cadherin and γ-catenin and their prognostic significance in pancreatic ductal adenocarcinoma (PDAC)

2018 ◽  
Vol 18 (3) ◽  
pp. 246-251 ◽  
Author(s):  
Petra Radulović ◽  
Božo Krušlin
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Patient Survival ◽  
Negative Impact ◽  
Prognostic Significance ◽  
Pancreatic Tissue ◽  
Ductal Adenocarcinoma ◽  
Clinicopathological Parameters ◽  
Rank Test ◽  
Normal Pancreatic Tissue ◽  
E Cadherin

Extensive research is being conducted to identify novel diagnostic, predictive and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC), as only a few markers have been routinely used so far with limited success. Our aim was to assess the expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), E-cadherin, and γ-catenin in PDAC in relation to clinicopathological parameters and patient survival. We also investigated if there is a correlation of NEDD9 expression with E-cadherin or γ-catenin. The protein expression was determined by immunohistochemistry in 61 PDAC and 61 samples of normal pancreatic tissue. The log rank test and Kaplan-Meier survival curve were used for survival analysis. E-cadherin and γ-catenin expressions were reduced in PDAC, and completely retained in normal pancreatic tissue. Expression of NEDD9 was significantly increased in PDAC (strong expression in 78.7% of cases and moderate in 21.3%) and reduced in normal pancreatic tissue (strong positivity in 45.9% of cases, moderate in 31.1%, and weak in 23%). There was a positive correlation between reduced E-cadherin and γ-catenin expression in PDAC (p = 0.015). The loss or reduced expression of E-cadherin had a negative impact on patient survival (p = 0.020). A negative correlation between E-cadherin expression and tumor grade was also observed (p = 0.011). Decreased E-cadherin expression was more common in male patients with PDAC (81.3% vs. 60% for females, p = 0.005). γ-catenin and NEDD9 expressions were not statistically correlated with tumor stage and grade, gender, nor with patient survival. Our results support the role of NEDD9, E-cadherin and γ-catenin proteins in PDAC, but further research should clarify in detail their mechanism of action in pancreatic cancer.

Prognostic Significance of Plasma Fibrinogen/Serum Albumin Ratio in the Postoperative Outcome of Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 40 (12) ◽  
pp. 7017-7023
Author(s):  
KOICHI TOMITA ◽  
SHIGETO OCHIAI ◽  
TAKAHIRO GUNJI ◽  
KOSUKE HIKITA ◽  
TOSHIMICHI KOBAYASHI ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Significance ◽  
Postoperative Outcome ◽  
Plasma Fibrinogen ◽  
Ductal Adenocarcinoma ◽  
Albumin Ratio

scholarly journals Liver Metastases in Newly Diagnosed Pancreatic Ductal Adenocarcinoma: A Population Based Analysis

2020 ◽  
Author(s):  
Guoyi Wu ◽  
Xiaoben Pan ◽  
Baohua Wang ◽  
Xiaolei Zhu ◽  
Jing Wu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Metastases ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Size ◽  
Cox Regression ◽  
Population Based ◽  
The Body ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Factors Associated

Abstract Background Estimates of the incidence and prognosis of developing liver metastases at the pancreatic ductal adenocarcinoma (PDAC) diagnosis are lacking.Methods In this study, we analyzed the association of liver metastases and the PDAC patients outcome. The risk factors associated with liver metastases in PDAC patients were analyzed using multivariable logistic regression analysis. The overall survival (OS) was estimated using Kaplan-Meier curves and log-rank test. Cox regression was performed to identify factors associated with OS.Results Patients with primary PDAC in the tail of the pancreas had a higher incidence of liver metastases (62.2%) than those with PDAC in the head (28.6%). Female gender, younger age, primary PDAC in the body or tail of the pancreas, and larger primary PDAC tumor size were positively associated with the occurrence of liver metastases. The median survival of patients with liver metastases was significantly shorter than that of patients without liver metastases. Older age, unmarried status, primary PDAC in the tail of the pancreas, and tumor size ≥4 cm were risk factors for OS in the liver metastases cohort.Conclusions Population-based estimates of the incidence and prognosis of PDAC with liver metastases may help decide whether diffusion-weighted magnetic resonance imaging should be performed in patients with primary PDAC in the tail or body of the pancreas. The location of primary PDAC should be considered during the diagnosis and treatment of primary PDAC.

scholarly journals Impact of Neoadjuvant Therapy in Resected Pancreatic Ductal Adenocarcinoma of the Pancreatic Body or Tail on Surgical and Oncological Outcome: A Propensity-Score Matched Multicenter Study

2019 ◽  
Vol 27 (6) ◽  
pp. 1986-1996 ◽  
Author(s):  
Sanne Lof ◽  
◽  
Maarten Korrel ◽  
Jony van Hilst ◽  
Adnan Alseidi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Fistula ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Neoadjuvant Therapy ◽  
Survival Benefit ◽  
Pancreatic Head ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Pancreatic Body ◽  
International Multicenter

Abstract Background Several studies have suggested a survival benefit of neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) in the pancreatic head. Data concerning NAT for PDAC located in pancreatic body or tail are lacking. Methods Post hoc analysis of an international multicenter retrospective cohort of distal pancreatectomy for PDAC in 34 centers from 11 countries (2007–2015). Patients who underwent resection after NAT were matched (1:1 ratio), using propensity scores based on baseline characteristics, to patients who underwent upfront resection. Median overall survival was compared using the stratified log-rank test. Results Among 1236 patients, 136 (11.0%) received NAT, most frequently FOLFIRINOX (25.7%). In total, 94 patients receiving NAT were matched to 94 patients undergoing upfront resection. NAT was associated with less postoperative major morbidity (Clavien–Dindo ≥ 3a, 10.6% vs. 23.4%, P = 0.020) and pancreatic fistula grade B/C (9.6% vs. 21.3%, P = 0.026). NAT did not improve overall survival [27 (95% CI 14–39) versus 31 months (95% CI 19–42), P = 0.277], as compared with upfront resection. In a sensitivity analysis of 251 patients with radiographic tumor involvement of splenic vessels, NAT (n = 37, 14.7%) was associated with prolonged overall survival [36 (95% CI 18–53) versus 20 months (95% CI 15–24), P = 0.049], as compared with upfront resection. Conclusion In this international multicenter cohort study, NAT for resected PDAC in pancreatic body or tail was associated with less morbidity and pancreatic fistula but similar overall survival in comparison with upfront resection. Prospective studies should confirm a survival benefit of NAT in patients with PDAC and splenic vessel involvement.

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