Identification of Key Genes Involved in Pancreatic Ductal Adenocarcinoma with Diabetes Mellitus Based on Gene Expression Profiling Analysis

This study aimed to identify key genes involved in the progression of diabetic pancreatic ductal adenocarcinoma (PDAC). Two gene expression datasets (GSE74629 and GSE15932) were obtained from Gene Expression Omnibus. Then, differentially expressed genes (DEGs) between diabetic PDAC and non-diabetic PDAC were identified, followed by a functional analysis. Subsequently, gene modules related to DM were extracted by weighed gene co-expression network analysis. The protein-protein interaction (PPI) network for genes in significant modules was constructed and functional analyses were also performed. After that, the optimal feature genes were screened by support vector machine (SVM) recursive feature elimination and SVM classification model was built. Finally, survival analysis was conducted to identify prognostic genes. The correlations between prognostic genes and other clinical factors were also analyzed. Totally, 1546 DEGs with consistent change tendencies were identified and functional analyses showed they were strongly correlated with metabolic pathways. Furthermore, there were two significant gene modules, in which RPS27A and UBA52 were key genes. Functional analysis of genes in two gene modules revealed that these genes primarily participated in oxidative phosphorylation pathway. Additionally, 21 feature genes were closely related with diabetic PDAC and the corresponding SVM classifier markedly distinguished diabetic PDAC from non-diabetic PDAC patients. Finally, decreased KIF22 and PYGL levels had good survival outcomes for PDAC. Four genes (RPS27A, UBA52, KIF22 and PYGL) might be involved in the pathogenesis of diabetic PDAC. Furthermore, KIF22 and PYGL acted as prognostic biomarkers for diabetic PDAC.

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Integrated Bioinformatics Analysis of Gene Expression Profiles for Potential Biomarker Identification Towards Early Therapeutic Intervention in Pancreatitis and Pancreatic Ductal Adenocarcinoma

10.21203/rs.3.rs-879048/v1 ◽

2021 ◽

Author(s):

Manoj M Wagle ◽

Ananya Rao Kedige ◽

Shama P Kabekkodu ◽

Sandeep Mallya

Keyword(s):

Gene Expression ◽

Pancreatic Ductal Adenocarcinoma ◽

Bioinformatics Analysis ◽

Ductal Adenocarcinoma ◽

Rapid Progression ◽

Hub Genes ◽

Altered Expression ◽

Biochemical Pathways ◽

Potential Biomarker ◽

Key Genes

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a malignancy associated with rapid progression and an abysmal prognosis. It has been reported that chronic pancreatitis can increase the risk of developing PDAC by 16-fold. Our study aims to identify the key genes and biochemical pathways mediating pancreatitis and PDAC. The gene expression datasets were retrieved from the EMBL-EBI ArrayExpress and NCBI GEO database. A total of 172 samples of normal pancreatic tissue, 68 samples of pancreatitis, and 306 samples of PDAC were used in this study. The differentially expressed genes (DEGs) identified were used to perform downstream analysis for ontology, interaction, and associated pathways. Furthermore, hub gene expression was validated using the GEPIA2 tool and survival analysis using the Kaplan-Meier (KM) plotter. The potential druggability of the hub genes identified was determined using the Drug-Gene Interaction Database (DGIdb). Our study identified a total of 45 genes found to have altered expression levels in both PDAC and pancreatitis. Over-representation analysis revealed that protein digestion and absorption pathway, ECM-receptor interaction pathway, PI3k-Akt signaling pathway, and proteoglycans in cancer pathways as significantly enriched. Module analysis revealed 15 hub genes with 92 edges, of which 14 were found to be in the druggable genome category. Through bioinformatics analysis, we identified key genes and biochemical pathways disrupted in pancreatitis and PDAC. The results can provide new insights into targeted therapy and intervening therapeutically at an earlier stage can be used as an effective strategy to decrease the incidence and severity of PDAC.

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Identification of the Roles of a Stemness Index Based on mRNA Expression in the Prognosis and Metabolic Reprograming of Pancreatic Ductal Adenocarcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.643465 ◽

2021 ◽

Vol 11 ◽

Author(s):

Rong Tang ◽

Xiaomeng Liu ◽

Wei Wang ◽

Jie Hua ◽

Jin Xu ◽

...

Keyword(s):

Stem Cells ◽

Mrna Expression ◽

Pancreatic Ductal Adenocarcinoma ◽

Metabolic Pathways ◽

Gene Set Enrichment Analysis ◽

Metabolic Reprogramming ◽

Ductal Adenocarcinoma ◽

Independent Gene ◽

Gene Modules ◽

Key Genes

BackgroundCancer stem cells (CSCs) are widely thought to contribute to the dismal prognosis of pancreatic ductal adenocarcinoma (PDAC). CSCs share biological features with adult stem cells, such as longevity, self-renewal capacity, differentiation, drug resistance, and the requirement for a niche; these features play a decisive role in cancer progression. A prominent characteristic of PDAC is metabolic reprogramming, which provides sufficient nutrients to support rapid tumor cell growth. However, whether PDAC stemness is correlated with metabolic reprogramming remains unknown.MethodRNA sequencing data of PDAC, including read counts and fragments per kilobase of transcript per million mapped reads (FPKM), were collected from The Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA-PAAD) database. Single-sample gene set enrichment analysis (GSEA) was used to calculate the relative activities of metabolic pathways in each PDAC sample. Quantitative real-time PCR was performed to validate the expression levels of genes of interest.ResultsThe overall survival (OS) of patients with high mRNA expression-based stemness index (mRNAsi) values was significantly worse than that of their counterparts with low mRNAsi values (P = 0.003). This survival disadvantage was independent of baseline clinical characteristics. Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and GSEA showed that the differentially expressed genes between patients with high and low mRNAsi values were mainly enriched in oncogenic and metabolic pathways. Weighted gene coexpression network analysis (WGCNA) revealed 8 independent gene modules that were significantly associated with mRNAsi and 12 metabolic pathways. Unsupervised clustering based on the key genes in each module identified two PDAC subgroups characterized by different mRNAsi values and metabolic activities. Univariate Cox regression analysis identified 14 genes beneficial to OS from 95 key genes selected from the eight independent gene modules from WGCNA. Among them, MAGEH1, MAP3K3, and PODN were downregulated in both pancreatic tissues and cell lines.ConclusionThe present study showed that PDAC samples with high mRNAsi values exhibited aberrant activation of multiple metabolic pathways, and the patients from whom these samples were obtained had a poor prognosis. Future studies are expected to investigate the underlying mechanism based on the crosstalk between PDAC stemness and metabolic rewiring.

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Predicting Hub Genes of Glioblastomas Based on Support Vector Machine Combined with CFS algorithms

Current Bioinformatics ◽

10.2174/1574893615999200819162140 ◽

2020 ◽

Vol 15 ◽

Author(s):

Chun Qiu ◽

Sai Li ◽

Shenghui Yang ◽

Lin Wang ◽

Aihui Zeng ◽

...

Keyword(s):

Support Vector Machine ◽

Expression Profiles ◽

Independent Set ◽

Classification Model ◽

Support Vector ◽

Feature Subset ◽

Hub Genes ◽

Effective Prevention ◽

Key Genes ◽

Control Samples

Aim: To search the genes related to the mechanisms of the occurrence of glioma and to try to build a prediction model for glioblastomas. Background: The morbidity and mortality of glioblastomas are very high, which seriously endangers human health. At present, the goals of many investigations on gliomas are mainly to understand the cause and mechanism of these tumors at the molecular level and to explore clinical diagnosis and treatment methods. However, there is no effective early diagnosis method for this disease, and there are no effective prevention, diagnosis or treatment measures. Methods: First, the gene expression profiles derived from GEO were downloaded. Then, differentially expressed genes (DEGs) in the disease samples and the control samples were identified. After that, GO and KEGG enrichment analyses of DEGs were performed by DAVID. Furthermore, the correlation-based feature subset (CFS) method was applied to the selection of key DEGs. In addition, the classification model between the glioblastoma samples and the controls was built by an Support Vector Machine (SVM) based on selected key genes. Results and Discussion: Thirty-six DEGs, including 17 upregulated and 19 downregulated genes, were selected as the feature genes to build the classification model between the glioma samples and the control samples by the CFS method. The accuracy of the classification model by using a 10-fold cross-validation test and independent set test was 76.25% and 70.3%, respectively. In addition, PPP2R2B and CYBB can also be found in the top 5 hub genes screened by the protein– protein interaction (PPI) network. Conclusions: This study indicated that the CFS method is a useful tool to identify key genes in glioblastomas. In addition, we also predicted that genes such as PPP2R2B and CYBB might be potential biomarkers for the diagnosis of glioblastomas.

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Discovering key transcriptomic regulators in pancreatic ductal adenocarcinoma using Dirichlet process Gaussian mixture model

Scientific Reports ◽

10.1038/s41598-021-87234-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sk Md Mosaddek Hossain ◽

Aanzil Akram Halsana ◽

Lutfunnesa Khatun ◽

Sumanta Ray ◽

Anirban Mukhopadhyay

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Mixture Model ◽

Cancer Progression ◽

Dirichlet Process ◽

Network Inference ◽

Correlation Method ◽

Gaussian Mixture ◽

Ductal Adenocarcinoma ◽

Gene Regulatory Network Inference ◽

Gene Modules

AbstractPancreatic Ductal Adenocarcinoma (PDAC) is the most lethal type of pancreatic cancer, late detection leading to its therapeutic failure. This study aims to determine the key regulatory genes and their impacts on the disease’s progression, helping the disease’s etiology, which is still mostly unknown. We leverage the landmark advantages of time-series gene expression data of this disease and thereby identified the key regulators that capture the characteristics of gene activity patterns in the cancer progression. We have identified the key gene modules and predicted the functions of top genes from a reconstructed gene association network (GAN). A variation of the partial correlation method is utilized to analyze the GAN, followed by a gene function prediction task. Moreover, we have identified regulators for each target gene by gene regulatory network inference using the dynamical GENIE3 (dynGENIE3) algorithm. The Dirichlet process Gaussian process mixture model and cubic spline regression model (splineTimeR) are employed to identify the key gene modules and differentially expressed genes, respectively. Our analysis demonstrates a panel of key regulators and gene modules that are crucial for PDAC disease progression.

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