scholarly journals In Silico Transcriptomic Analysis of the Chloride Intracellular Channels (CLIC) Interactome Identifies a Molecular Panel of Seven Prognostic Markers in Patients with Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 21 (2) ◽  
pp. 119-127
Author(s):  
Dimitrios E. Magouliotis ◽  
Nikos Sakellaridis ◽  
Konstantinos Dimas ◽  
Vasiliki S. Tasiopoulou ◽  
Konstantina A. Svokos ◽  
...  

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. In this context, the identification of biomarkers regarding the PDAC diagnosis, monitoring, and prognosis is crucial. Objectives: The purpose of the current study was to investigate the differential gene expression profile of the chloride intracellular channel (CLIC) gene family network in patients with PDAC, in order to suggest novel biomarkers. Methods: In silico techniques were used to construct the interactome of the CLIC gene family, identify the differentially expressed genes (DEGs) in PDAC as compared to healthy controls, and evaluate their potential prognostic role. Results: Transcriptomic data of three microarray datasets were included, incorporating 114 tumor and 59 normal pancreatic samples. Twenty DEGs were identified; eight were up-regulated and twelve were downregulated. A molecular signature of seven genes (Chloride Intracellular Channel 1 – CLIC1; Chloride Intracellular Channel 3 – CLIC3; Chloride Intracellular Channel 4 – CLIC4; Ganglioside Induced Differentiation Associated Protein 1 – GDAP1; Ganglioside Induced Differentiation Associated Protein 1 Like 1 – GDAP1L1; Glutathione S-Transferase Pi 1 - GSTP1; Prostaglandin E Synthase 2 – PTGES2) were identified as prognostic markers associated with overall survival. Positive correlations were reported regarding the expression of CLIC1-CLIC3, CLIC4-CLIC5, and CLIC5- CLIC6. Finally, gene set enrichment analysis demonstrated the molecular functions and miRNA families (hsa-miR-122, hsa-miR-618, hsa-miR-425, and hsa-miR-518) relevant to the seven prognostic markers. Conclusions: These outcomes demonstrate a seven-gene molecular panel that predicts the patients’ prospective survival following pancreatic resection for PDAC.

Pancreatology ◽  
2019 ◽  
Vol 19 (3) ◽  
pp. 436-442 ◽  
Author(s):  
Dimitrios E. Magouliotis ◽  
Vasiliki S. Tasiopoulou ◽  
Konstantinos Dimas ◽  
Nikos Sakellaridis ◽  
Konstantina A. Svokos ◽  
...  

Oncotarget ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 145-159
Author(s):  
Eric Russ ◽  
Krithika Bhuvaneshwar ◽  
Guisong Wang ◽  
Benjamin Jin ◽  
Michele M. Gage ◽  
...  

2017 ◽  
Vol Volume 10 ◽  
pp. 4493-4506 ◽  
Author(s):  
Xiwen Liao ◽  
Ketuan Huang ◽  
Rui Huang ◽  
Xiaoguang Liu ◽  
Chuangye Han ◽  
...  

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jun-Qi Liu ◽  
Xi-Wen Liao ◽  
Xiang-Kun Wang ◽  
Cheng-Kun Yang ◽  
Xin Zhou ◽  
...  

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.


2016 ◽  
Vol 45 (7) ◽  
pp. 749-763 ◽  
Author(s):  
A. Zaccagnino ◽  
C. Pilarsky ◽  
D. Tawfik ◽  
S. Sebens ◽  
A. Trauzold ◽  
...  

2020 ◽  
Author(s):  
Peng Xu ◽  
Dong Xiao Wang ◽  
Nan Zheng Li ◽  
Jun Jian Qian ◽  
Jie Yao ◽  
...  

Abstract Background: To explore significance of CA19-9, D-dimer with TNFAIP3 (A20) protein and evaluate its prognostic significance in patients suffering from pancreatic ductal adenocarcinoma (PDAC). Methods: 148 patients suffering from pancreatic ductal adenocarcinoma in Northern Jiangsu People’s Hospital affiliated to Yangzhou University between January 2012 to December 2016 were studied. Cutoff values of prognostic factors were predicted by Receiver operating characteristic curve (ROC curve). Kaplan-Meier method was used to describe survival curve of patients. Univariate and multivariate regression analyses were used to analyze prognostic factors of patients. Results: The recommended cutoff values of the neutrophil-lymphocyte rate (NLR), platelet-lymphocyte rate (PLR), CA19-9 and D-dimer were 2.04 (sensitivity, 0.59; specificity, 0.9; area under the ROC curve (AUC), 0.749; P<0.001), 52.94 (sensitivity, 0.73; specificity, 0.95; AUC, 0.829; P<0.001), 176.66U/ml (sensitivity, 0.7; specificity, 0.9; AUC, 0.794; P<0.001) and 1.18mg/L (sensitivity, 0.82; specificity, 0.9; AUC, 0.845; P<0.001) respectively. The expression of CA19-9 in serum was related with lymph node metastasis (P = 0.010), tumor lymph node metastasis (TNM) stage (P <0.001) and survival ratio (P <0.001). The D-dimer was positively related with differentiation grade (P=0.014), tumor size (P=0.045), TNM stage (P=0.006) and survival ratio (P<0.001). A20 was positively related with differentiation grade (P<0.001), BMI (P<0.001), TNM stage (P=0.024) and survival ratio (P<0.001). The Kaplan-Meier curves showed that the patients with pancreatic ductal adenocarcinoma had a significant difference in the expression of CA19-9 group, expression of D-dimer group and expression of A20 (P<0.05). CA19-9, D-dimer, TNM stage, differentiation grade and A20 were independent prognostic markers for patients sufferingfrom pancreatic ductal adenocarcinoma by univariate and COX multivariate analyses. Conclusions: CA19-9, D-dimer and A20 were independent prognostic markers for pancreatic ductal adenocarcinoma patients.


Author(s):  
O. I. Kit ◽  
E. M. Franciyanc ◽  
I. S. Derizhanova ◽  
N. S. Karnaukhov ◽  
M. A. Kuznetsova ◽  
...  

Purpose of the study. Determine the frequency of MiNeN among pancreatic carcinomas and analyze the survival rate of patients depending on the percentage of cells with neuroendocrine differentiation in the tumor.Materials and methods. The current study included 31 patients with a pancreatic tumor who received surgical treatment at the Rostov Cancer Research Institute. An immunohistochemical study was conducted on biomarkers of chromogranin A, synaptophysin, and ki-67 for these patients. Based on the data obtained, 4 groups for neuroendocrine differentiation were identified.Results. The direct effect of neuroendocrine differentiation on the survival of patients with histologically confirmed pancreatic ductal adenocarcinoma has been proven. Among the sample of 31 patients, neuroendocrine differentiation was revealed in 24 cases (77%), of which 3 cases of MiNeN (10.3%) were detected. It is also proven relationship between neuroendocrine and patient survival, where an increase percent of positive cells in tumors (chromogranin A or synaptophysin) means a better prognosis. Chromogranin A is a more significant predictor of survival compared to synaptophysin. The largest difference in survival was between negative expression of chromogranin A and the presence of more than 1% positive cells in the tumor.Conclusion. We supposed that it is necessary to use neuroendocrine markers (chromogranin A and synaptophysin) in the diagnosis of ductal adenocarcinomas, even without histological signs of neuroendocrine differentiation. This will allow for a larger amount of data to determine their significance as prognostic markers.


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