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Bioinformatics-based construction of prognosis-related methylation prediction model for pancreatic cancer patients and its application value

Objective: Pancreatic adenocarcinoma (PAAD) is a highly malignant gastrointestinal tumor with almost similar morbidity and mortality. In this study, based on bioinformatics, we investigated the role of gene methylation in PAAD, evaluated relevant factors affecting patient prognosis, screened potenti...

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Autores principales: Cao, Tiansheng, Wu, Hongsheng, Ji, Tengfei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034005/
https://www.ncbi.nlm.nih.gov/pubmed/36969862
http://dx.doi.org/10.3389/fphar.2023.1086309
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author Cao, Tiansheng
Wu, Hongsheng
Ji, Tengfei
author_facet Cao, Tiansheng
Wu, Hongsheng
Ji, Tengfei
author_sort Cao, Tiansheng
collection PubMed
description Objective: Pancreatic adenocarcinoma (PAAD) is a highly malignant gastrointestinal tumor with almost similar morbidity and mortality. In this study, based on bioinformatics, we investigated the role of gene methylation in PAAD, evaluated relevant factors affecting patient prognosis, screened potential anti-cancer small molecule drugs, and constructed a prediction model to assess the prognosis of PAAD. Methods: Clinical and genomic data of PAAD were collected from the Tumor Genome Atlas Project (TCGA) database and gene expression profiles were obtained from the GTEX database. Analysis of differentially methylated genes (DMGs) and significantly differentially expressed genes (DEGs) was performed on tumorous samples with KRAS wild-type and normal samples using the “limma” package and combined analysis. We selected factors significantly associated with survival from the significantly differentially methylated and expressed genes (DMEGs), and their fitting into a relatively streamlined prognostic model was validated separately from the internal training and test sets and the external ICGC database to show the robustness of the model. Results: In the TCGA database, 2,630 DMGs were identified, with the largest gap between DMGs in the gene body and TSS200 region. 318 DEGs were screened, and the enrichment analysis of DMGs and DEGs was taken to intersect DMEGs, showing that the DMEGs were mainly related to Olfactory transduction, natural killer cell mediated cytotoxicity pathway, and Cytokine -cytokine receptor interaction. DMEGs were able to distinguish well between PAAD and paraneoplastic tissues. Through techniques such as drug database and molecular docking, we screened a total of 10 potential oncogenic small molecule compounds, among which felbamate was the most likely target drug for PAAD. We constructed a risk model through combining three DMEGs (S100P, LY6D, and WFDC13) with clinical factors significantly associated with prognosis, and confirmed the model robustness using external and internal validation. Conclusion: The classification model based on DMEGs was able to accurately separate normal samples from tumor samples and find potential anti-PAAD drugs by performing gene-drug interactions on DrugBank.
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spelling pubmed-100340052023-03-24 Bioinformatics-based construction of prognosis-related methylation prediction model for pancreatic cancer patients and its application value Cao, Tiansheng Wu, Hongsheng Ji, Tengfei Front Pharmacol Pharmacology Objective: Pancreatic adenocarcinoma (PAAD) is a highly malignant gastrointestinal tumor with almost similar morbidity and mortality. In this study, based on bioinformatics, we investigated the role of gene methylation in PAAD, evaluated relevant factors affecting patient prognosis, screened potential anti-cancer small molecule drugs, and constructed a prediction model to assess the prognosis of PAAD. Methods: Clinical and genomic data of PAAD were collected from the Tumor Genome Atlas Project (TCGA) database and gene expression profiles were obtained from the GTEX database. Analysis of differentially methylated genes (DMGs) and significantly differentially expressed genes (DEGs) was performed on tumorous samples with KRAS wild-type and normal samples using the “limma” package and combined analysis. We selected factors significantly associated with survival from the significantly differentially methylated and expressed genes (DMEGs), and their fitting into a relatively streamlined prognostic model was validated separately from the internal training and test sets and the external ICGC database to show the robustness of the model. Results: In the TCGA database, 2,630 DMGs were identified, with the largest gap between DMGs in the gene body and TSS200 region. 318 DEGs were screened, and the enrichment analysis of DMGs and DEGs was taken to intersect DMEGs, showing that the DMEGs were mainly related to Olfactory transduction, natural killer cell mediated cytotoxicity pathway, and Cytokine -cytokine receptor interaction. DMEGs were able to distinguish well between PAAD and paraneoplastic tissues. Through techniques such as drug database and molecular docking, we screened a total of 10 potential oncogenic small molecule compounds, among which felbamate was the most likely target drug for PAAD. We constructed a risk model through combining three DMEGs (S100P, LY6D, and WFDC13) with clinical factors significantly associated with prognosis, and confirmed the model robustness using external and internal validation. Conclusion: The classification model based on DMEGs was able to accurately separate normal samples from tumor samples and find potential anti-PAAD drugs by performing gene-drug interactions on DrugBank. Frontiers Media S.A. 2023-03-09 /pmc/articles/PMC10034005/ /pubmed/36969862 http://dx.doi.org/10.3389/fphar.2023.1086309 Text en Copyright © 2023 Cao, Wu and Ji. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Cao, Tiansheng
Wu, Hongsheng
Ji, Tengfei
Bioinformatics-based construction of prognosis-related methylation prediction model for pancreatic cancer patients and its application value
title Bioinformatics-based construction of prognosis-related methylation prediction model for pancreatic cancer patients and its application value
title_full Bioinformatics-based construction of prognosis-related methylation prediction model for pancreatic cancer patients and its application value
title_fullStr Bioinformatics-based construction of prognosis-related methylation prediction model for pancreatic cancer patients and its application value
title_full_unstemmed Bioinformatics-based construction of prognosis-related methylation prediction model for pancreatic cancer patients and its application value
title_short Bioinformatics-based construction of prognosis-related methylation prediction model for pancreatic cancer patients and its application value
title_sort bioinformatics-based construction of prognosis-related methylation prediction model for pancreatic cancer patients and its application value
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034005/
https://www.ncbi.nlm.nih.gov/pubmed/36969862
http://dx.doi.org/10.3389/fphar.2023.1086309
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