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Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma

OBJECTIVE: The main reasons for the poor prognoses of pancreatic adenocarcinoma (PA) patients are rapid early-stage progression, advanced stage metastasis, and chemotherapy resistance. Identification of novel diagnostic and prognostic biomarkers of PA is therefore urgently needed. METHODS: Three mRN...

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Autores principales: Zuo, Duo, Chen, Yongzi, Zhang, Xinwei, Wang, Zhuozhi, Jiang, Wenna, Tang, Fan, Cheng, Runfen, Sun, Yi, Sun, Lu, Ren, Li, Liu, Rui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Compuscript 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334760/
https://www.ncbi.nlm.nih.gov/pubmed/34403221
http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0516
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author Zuo, Duo
Chen, Yongzi
Zhang, Xinwei
Wang, Zhuozhi
Jiang, Wenna
Tang, Fan
Cheng, Runfen
Sun, Yi
Sun, Lu
Ren, Li
Liu, Rui
author_facet Zuo, Duo
Chen, Yongzi
Zhang, Xinwei
Wang, Zhuozhi
Jiang, Wenna
Tang, Fan
Cheng, Runfen
Sun, Yi
Sun, Lu
Ren, Li
Liu, Rui
author_sort Zuo, Duo
collection PubMed
description OBJECTIVE: The main reasons for the poor prognoses of pancreatic adenocarcinoma (PA) patients are rapid early-stage progression, advanced stage metastasis, and chemotherapy resistance. Identification of novel diagnostic and prognostic biomarkers of PA is therefore urgently needed. METHODS: Three mRNA microarray datasets were obtained from the Gene Expression Omnibus database to select differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for hub genes were performed using DAVID. Correlations between expression levels of hub genes and cancer-infiltrating immune cells were investigated by TIMER. Cox proportional hazard regression analyses were also performed. Serum hub genes were screened using the HPA platform and verified for diagnostic value using ELISAs. RESULTS: We identified 59 hub genes among 752 DEGs. GO analysis indicated that these 59 hub genes were mainly involved in the defense response to viruses and the type I interferon signaling pathway. We also discovered that RSAD2 and SMC4 were associated with immune cell infiltration in the PA microenvironment. Additionally, DLGAP5 mRNA might be used as an independent risk factor for the prognoses of PA patients. Furthermore, the protein encoded by ISG15, which exists in peripheral blood, was validated as a potential diagnostic biomarker that distinguished PA patients from healthy controls (area under the curve: 0.902, 95% confidence interval: 0.819–0.961). CONCLUSIONS: Our study suggested that RSAD2 and SMC4 were associated with immune cell infiltration in the PA microenvironment, while DLGAP5 mRNA expression might be an independent risk factor for the survival prognoses of PA patients. Moreover, ELISAs indicated that serum ISG15 could be a potential novel diagnostic biomarker for PA.
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spelling pubmed-93347602022-08-09 Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma Zuo, Duo Chen, Yongzi Zhang, Xinwei Wang, Zhuozhi Jiang, Wenna Tang, Fan Cheng, Runfen Sun, Yi Sun, Lu Ren, Li Liu, Rui Cancer Biol Med Original Article OBJECTIVE: The main reasons for the poor prognoses of pancreatic adenocarcinoma (PA) patients are rapid early-stage progression, advanced stage metastasis, and chemotherapy resistance. Identification of novel diagnostic and prognostic biomarkers of PA is therefore urgently needed. METHODS: Three mRNA microarray datasets were obtained from the Gene Expression Omnibus database to select differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for hub genes were performed using DAVID. Correlations between expression levels of hub genes and cancer-infiltrating immune cells were investigated by TIMER. Cox proportional hazard regression analyses were also performed. Serum hub genes were screened using the HPA platform and verified for diagnostic value using ELISAs. RESULTS: We identified 59 hub genes among 752 DEGs. GO analysis indicated that these 59 hub genes were mainly involved in the defense response to viruses and the type I interferon signaling pathway. We also discovered that RSAD2 and SMC4 were associated with immune cell infiltration in the PA microenvironment. Additionally, DLGAP5 mRNA might be used as an independent risk factor for the prognoses of PA patients. Furthermore, the protein encoded by ISG15, which exists in peripheral blood, was validated as a potential diagnostic biomarker that distinguished PA patients from healthy controls (area under the curve: 0.902, 95% confidence interval: 0.819–0.961). CONCLUSIONS: Our study suggested that RSAD2 and SMC4 were associated with immune cell infiltration in the PA microenvironment, while DLGAP5 mRNA expression might be an independent risk factor for the survival prognoses of PA patients. Moreover, ELISAs indicated that serum ISG15 could be a potential novel diagnostic biomarker for PA. Compuscript 2022-07-15 2021-08-17 /pmc/articles/PMC9334760/ /pubmed/34403221 http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0516 Text en Copyright: © 2022, Cancer Biology & Medicine 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) 4.0 (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
spellingShingle Original Article
Zuo, Duo
Chen, Yongzi
Zhang, Xinwei
Wang, Zhuozhi
Jiang, Wenna
Tang, Fan
Cheng, Runfen
Sun, Yi
Sun, Lu
Ren, Li
Liu, Rui
Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma
title Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma
title_full Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma
title_fullStr Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma
title_full_unstemmed Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma
title_short Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma
title_sort identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334760/
https://www.ncbi.nlm.nih.gov/pubmed/34403221
http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0516
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