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Identification of Key Genes in Lung Adenocarcinoma and Establishment of Prognostic Mode

BACKGROUND: The development of human tumors is associated with the abnormal expression of various functional genes, and a massive tumor-based database needs to be deeply mined. Based on a multigene prediction model, access to urgent prognosis of patients has become possible. MATERIALS AND METHODS: W...

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Autores principales: Jiawei, Zhou, Min, Mu, Yingru, Xing, Xin, Zhang, Danting, Li, Yafeng, Liu, Jun, Xie, Wangfa, Hu, Lijun, Zhang, Jing, Wu, Dong, Hu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653064/
https://www.ncbi.nlm.nih.gov/pubmed/33195408
http://dx.doi.org/10.3389/fmolb.2020.561456
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author Jiawei, Zhou
Min, Mu
Yingru, Xing
Xin, Zhang
Danting, Li
Yafeng, Liu
Jun, Xie
Wangfa, Hu
Lijun, Zhang
Jing, Wu
Dong, Hu
author_facet Jiawei, Zhou
Min, Mu
Yingru, Xing
Xin, Zhang
Danting, Li
Yafeng, Liu
Jun, Xie
Wangfa, Hu
Lijun, Zhang
Jing, Wu
Dong, Hu
author_sort Jiawei, Zhou
collection PubMed
description BACKGROUND: The development of human tumors is associated with the abnormal expression of various functional genes, and a massive tumor-based database needs to be deeply mined. Based on a multigene prediction model, access to urgent prognosis of patients has become possible. MATERIALS AND METHODS: We selected three RNA expression profiles (GSE32863, GSE10072, and GSE43458) from the lung adenocarcinoma (LUAD) database of the Gene Expression Omnibus (GEO) and analyzed the differentially expressed genes (DEGs) between tumor and normal tissue using GEO2R program. After that, we analyzed the transcriptome data of 479 LUAD samples (54 normal tissue samples and 425 cancer tissue samples) and their clinical follow-up data from the (TCGA) database. Kaplan–Meier (KM) curve and receiver operating characteristic (ROC) were used to assess the prediction model. Multivariate Cox analysis was used to identify independent predictors. TCGA pancreatic adenocarcinoma datasets were used to establish a nomogram model. RESULTS: We found 98 significantly prognosis-related genes using KM and COX analysis, among which six genes were found to be the DEGs in GEO. Using multivariate analysis, it was found that a single gene could not be used as an independent predictor of prognosis. However, the risk score calculated by weighting these six genes could serve as an independent prognosis predictor. COX analysis performed with multiple covariates such as age, gender, tumor stage, and TNM typing showed that risk score could still be utilized as an independent risk factor for patient survival rate (p = 0.013) and had an applicable reliability (area under the curve, AUC = 0.665). By combining risk score and various clinical features, the nomogram model was constructed, which had been proven to have high consistency for the prediction of 3- and 5-year survival rate (concordance = 0.751) and high accuracy as tested by ROC (AUC = 0.71;AUC = 0.708). CONCLUSION: We proposed a method to predict the prognosis of LUAD by weighting multiple genes and constructed a nomogram model suitable for the prognostic evaluation of LUAD, which could provide a new tool for the identification of therapeutic targets and the efficacy evaluation of LUAD.
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spelling pubmed-76530642020-11-13 Identification of Key Genes in Lung Adenocarcinoma and Establishment of Prognostic Mode Jiawei, Zhou Min, Mu Yingru, Xing Xin, Zhang Danting, Li Yafeng, Liu Jun, Xie Wangfa, Hu Lijun, Zhang Jing, Wu Dong, Hu Front Mol Biosci Molecular Biosciences BACKGROUND: The development of human tumors is associated with the abnormal expression of various functional genes, and a massive tumor-based database needs to be deeply mined. Based on a multigene prediction model, access to urgent prognosis of patients has become possible. MATERIALS AND METHODS: We selected three RNA expression profiles (GSE32863, GSE10072, and GSE43458) from the lung adenocarcinoma (LUAD) database of the Gene Expression Omnibus (GEO) and analyzed the differentially expressed genes (DEGs) between tumor and normal tissue using GEO2R program. After that, we analyzed the transcriptome data of 479 LUAD samples (54 normal tissue samples and 425 cancer tissue samples) and their clinical follow-up data from the (TCGA) database. Kaplan–Meier (KM) curve and receiver operating characteristic (ROC) were used to assess the prediction model. Multivariate Cox analysis was used to identify independent predictors. TCGA pancreatic adenocarcinoma datasets were used to establish a nomogram model. RESULTS: We found 98 significantly prognosis-related genes using KM and COX analysis, among which six genes were found to be the DEGs in GEO. Using multivariate analysis, it was found that a single gene could not be used as an independent predictor of prognosis. However, the risk score calculated by weighting these six genes could serve as an independent prognosis predictor. COX analysis performed with multiple covariates such as age, gender, tumor stage, and TNM typing showed that risk score could still be utilized as an independent risk factor for patient survival rate (p = 0.013) and had an applicable reliability (area under the curve, AUC = 0.665). By combining risk score and various clinical features, the nomogram model was constructed, which had been proven to have high consistency for the prediction of 3- and 5-year survival rate (concordance = 0.751) and high accuracy as tested by ROC (AUC = 0.71;AUC = 0.708). CONCLUSION: We proposed a method to predict the prognosis of LUAD by weighting multiple genes and constructed a nomogram model suitable for the prognostic evaluation of LUAD, which could provide a new tool for the identification of therapeutic targets and the efficacy evaluation of LUAD. Frontiers Media S.A. 2020-10-27 /pmc/articles/PMC7653064/ /pubmed/33195408 http://dx.doi.org/10.3389/fmolb.2020.561456 Text en Copyright © 2020 Jiawei, Min, Yingru, Xin, Danting, Yafeng, Jun, Wangfa, Lijun, Jing and Dong. http://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 Molecular Biosciences
Jiawei, Zhou
Min, Mu
Yingru, Xing
Xin, Zhang
Danting, Li
Yafeng, Liu
Jun, Xie
Wangfa, Hu
Lijun, Zhang
Jing, Wu
Dong, Hu
Identification of Key Genes in Lung Adenocarcinoma and Establishment of Prognostic Mode
title Identification of Key Genes in Lung Adenocarcinoma and Establishment of Prognostic Mode
title_full Identification of Key Genes in Lung Adenocarcinoma and Establishment of Prognostic Mode
title_fullStr Identification of Key Genes in Lung Adenocarcinoma and Establishment of Prognostic Mode
title_full_unstemmed Identification of Key Genes in Lung Adenocarcinoma and Establishment of Prognostic Mode
title_short Identification of Key Genes in Lung Adenocarcinoma and Establishment of Prognostic Mode
title_sort identification of key genes in lung adenocarcinoma and establishment of prognostic mode
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653064/
https://www.ncbi.nlm.nih.gov/pubmed/33195408
http://dx.doi.org/10.3389/fmolb.2020.561456
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