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Integrated transcriptomic analysis reveals hub genes involved in diagnosis and prognosis of pancreatic cancer

BACKGROUND: The hunt for the molecular markers with specificity and sensitivity has been a hot area for the tumor treatment. Due to the poor diagnosis and prognosis of pancreatic cancer (PC), the excision rate is often low, which makes it more urgent to find the ideal tumor markers. METHODS: Robust...

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Autores principales: Zhou, Yang-Yang, Chen, Li-Ping, Zhang, Yi, Hu, Sun-Kuan, Dong, Zhao-Jun, Wu, Ming, Chen, Qiu-Xiang, Zhuang, Zhi-Zhi, Du, Xiao-Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842480/
https://www.ncbi.nlm.nih.gov/pubmed/31706267
http://dx.doi.org/10.1186/s10020-019-0113-2
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author Zhou, Yang-Yang
Chen, Li-Ping
Zhang, Yi
Hu, Sun-Kuan
Dong, Zhao-Jun
Wu, Ming
Chen, Qiu-Xiang
Zhuang, Zhi-Zhi
Du, Xiao-Jing
author_facet Zhou, Yang-Yang
Chen, Li-Ping
Zhang, Yi
Hu, Sun-Kuan
Dong, Zhao-Jun
Wu, Ming
Chen, Qiu-Xiang
Zhuang, Zhi-Zhi
Du, Xiao-Jing
author_sort Zhou, Yang-Yang
collection PubMed
description BACKGROUND: The hunt for the molecular markers with specificity and sensitivity has been a hot area for the tumor treatment. Due to the poor diagnosis and prognosis of pancreatic cancer (PC), the excision rate is often low, which makes it more urgent to find the ideal tumor markers. METHODS: Robust Rank Aggreg (RRA) methods was firstly applied to identify the differentially expressed genes (DEGs) between PC tissues and normal tissues from GSE28735, GSE15471, GSE16515, and GSE101448. Among these DEGs, the highly correlated genes were clustered using WGCNA analysis. The co-expression networks and molecular complex detection (MCODE) Cytoscape app were then performed to find the sub-clusters and confirm 35 candidate genes. For these genes, least absolute shrinkage and selection operator (lasso) regression model was applied and validated to build a diagnostic risk score model. Cox proportional hazard regression analysis was used and validated to build a prognostic model. RESULTS: Based on integrated transcriptomic analysis, we identified a 19 gene module (SYCN, PNLIPRP1, CAP2, GNMT, MAT1A, ABAT, GPT2, ADHFE1, PHGDH, PSAT1, ERP27, PDIA2, MT1H, COMP, COL5A2, FN1, COL1A2, FAP and POSTN) as a specific predictive signature for the diagnosis of PC. Based on the two consideration, accuracy and feasibility, we simplified the diagnostic risk model as a four-gene model: 0.3034*log(2)(MAT1A)-0.1526*log(2)(MT1H) + 0.4645*log(2)(FN1) -0.2244*log(2)(FAP), log(2)(gene count). Besides, a four-hub gene module was also identified as prognostic model = − 1.400*log(2)(CEL) + 1.321*log(2)(CPA1) + 0.454*log(2)(POSTN) + 1.011*log(2)(PM20D1), log(2)(gene count). CONCLUSION: Integrated transcriptomic analysis identifies two four-hub gene modules as specific predictive signatures for the diagnosis and prognosis of PC, which may bring new sight for the clinical practice of PC.
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spelling pubmed-68424802019-11-14 Integrated transcriptomic analysis reveals hub genes involved in diagnosis and prognosis of pancreatic cancer Zhou, Yang-Yang Chen, Li-Ping Zhang, Yi Hu, Sun-Kuan Dong, Zhao-Jun Wu, Ming Chen, Qiu-Xiang Zhuang, Zhi-Zhi Du, Xiao-Jing Mol Med Research Article BACKGROUND: The hunt for the molecular markers with specificity and sensitivity has been a hot area for the tumor treatment. Due to the poor diagnosis and prognosis of pancreatic cancer (PC), the excision rate is often low, which makes it more urgent to find the ideal tumor markers. METHODS: Robust Rank Aggreg (RRA) methods was firstly applied to identify the differentially expressed genes (DEGs) between PC tissues and normal tissues from GSE28735, GSE15471, GSE16515, and GSE101448. Among these DEGs, the highly correlated genes were clustered using WGCNA analysis. The co-expression networks and molecular complex detection (MCODE) Cytoscape app were then performed to find the sub-clusters and confirm 35 candidate genes. For these genes, least absolute shrinkage and selection operator (lasso) regression model was applied and validated to build a diagnostic risk score model. Cox proportional hazard regression analysis was used and validated to build a prognostic model. RESULTS: Based on integrated transcriptomic analysis, we identified a 19 gene module (SYCN, PNLIPRP1, CAP2, GNMT, MAT1A, ABAT, GPT2, ADHFE1, PHGDH, PSAT1, ERP27, PDIA2, MT1H, COMP, COL5A2, FN1, COL1A2, FAP and POSTN) as a specific predictive signature for the diagnosis of PC. Based on the two consideration, accuracy and feasibility, we simplified the diagnostic risk model as a four-gene model: 0.3034*log(2)(MAT1A)-0.1526*log(2)(MT1H) + 0.4645*log(2)(FN1) -0.2244*log(2)(FAP), log(2)(gene count). Besides, a four-hub gene module was also identified as prognostic model = − 1.400*log(2)(CEL) + 1.321*log(2)(CPA1) + 0.454*log(2)(POSTN) + 1.011*log(2)(PM20D1), log(2)(gene count). CONCLUSION: Integrated transcriptomic analysis identifies two four-hub gene modules as specific predictive signatures for the diagnosis and prognosis of PC, which may bring new sight for the clinical practice of PC. BioMed Central 2019-11-09 /pmc/articles/PMC6842480/ /pubmed/31706267 http://dx.doi.org/10.1186/s10020-019-0113-2 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhou, Yang-Yang
Chen, Li-Ping
Zhang, Yi
Hu, Sun-Kuan
Dong, Zhao-Jun
Wu, Ming
Chen, Qiu-Xiang
Zhuang, Zhi-Zhi
Du, Xiao-Jing
Integrated transcriptomic analysis reveals hub genes involved in diagnosis and prognosis of pancreatic cancer
title Integrated transcriptomic analysis reveals hub genes involved in diagnosis and prognosis of pancreatic cancer
title_full Integrated transcriptomic analysis reveals hub genes involved in diagnosis and prognosis of pancreatic cancer
title_fullStr Integrated transcriptomic analysis reveals hub genes involved in diagnosis and prognosis of pancreatic cancer
title_full_unstemmed Integrated transcriptomic analysis reveals hub genes involved in diagnosis and prognosis of pancreatic cancer
title_short Integrated transcriptomic analysis reveals hub genes involved in diagnosis and prognosis of pancreatic cancer
title_sort integrated transcriptomic analysis reveals hub genes involved in diagnosis and prognosis of pancreatic cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842480/
https://www.ncbi.nlm.nih.gov/pubmed/31706267
http://dx.doi.org/10.1186/s10020-019-0113-2
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