Comprehensive Analysis of a Nine-Gene Signature Related to Tumor Microenvironment in Lung Adenocarcinoma
Lung adenocarcinoma (LUAD) is the most common malignancy, leading to more than 1 million related deaths each year. Due to low long-term survival rates, the exploration of molecular mechanisms underlying LUAD progression and novel prognostic predictors is urgently needed to improve LUAD treatment. In...
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doaj-1e5a63ffb6df47169449e6f5ba86c00d2021-09-03T23:38:53ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-09-01910.3389/fcell.2021.700607700607Comprehensive Analysis of a Nine-Gene Signature Related to Tumor Microenvironment in Lung AdenocarcinomaHaihui Zhong0Jie Wang1Yaru Zhu2Yefeng Shen3Department of Thoracic Surgery, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou Academy of Medical Sciences, Meizhou, ChinaInstitute for Pathology, University Hospital of Cologne, Cologne, GermanyDepartment of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaInstitute for Pathology, University Hospital of Cologne, Cologne, GermanyLung adenocarcinoma (LUAD) is the most common malignancy, leading to more than 1 million related deaths each year. Due to low long-term survival rates, the exploration of molecular mechanisms underlying LUAD progression and novel prognostic predictors is urgently needed to improve LUAD treatment. In our study, cancer-specific differentially expressed genes (DEGs) were identified using the robust rank aggregation (RRA) method between tumor and normal tissues from six Gene Expression Omnibus databases (GSE43458, GSE62949, GSE68465, GSE115002, GSE116959, and GSE118370), followed by a selection of prognostic modules using weighted gene co-expression network analysis. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were applied to identify nine hub genes (CBFA2T3, CR2, SEL1L3, TM6SF1, TSPAN32, ITGA6, MAPK11, RASA3, and TLR6) that constructed a prognostic risk model. The RNA expressions of nine hub genes were validated in tumor and normal tissues by RNA-sequencing and single-cell RNA-sequencing, while immunohistochemistry staining from the Human Protein Atlas database showed consistent results in the protein levels. The risk model revealed that high-risk patients were associated with poor prognoses, including advanced stages and low survival rates. Furthermore, a multivariate Cox regression analysis suggested that the prognostic risk model could be an independent prognostic factor for LUAD patients. A nomogram that incorporated the signature and clinical features was additionally built for prognostic prediction. Moreover, the levels of hub genes were related to immune cell infiltration in LUAD microenvironments. A CMap analysis identified 13 small molecule drugs as potential agents based on the risk model for LUAD treatment. Thus, we identified a prognostic risk model including CBFA2T3, CR2, SEL1L3, TM6SF1, TSPAN32, ITGA6, MAPK11, RASA3, and TLR6 as novel biomarkers and validated their prognostic and predicted values for LUAD.https://www.frontiersin.org/articles/10.3389/fcell.2021.700607/fulltumor microenvironmentlung adenocarcinomabiomarkerdiagnosisprognosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Haihui Zhong Jie Wang Yaru Zhu Yefeng Shen |
spellingShingle |
Haihui Zhong Jie Wang Yaru Zhu Yefeng Shen Comprehensive Analysis of a Nine-Gene Signature Related to Tumor Microenvironment in Lung Adenocarcinoma Frontiers in Cell and Developmental Biology tumor microenvironment lung adenocarcinoma biomarker diagnosis prognosis |
author_facet |
Haihui Zhong Jie Wang Yaru Zhu Yefeng Shen |
author_sort |
Haihui Zhong |
title |
Comprehensive Analysis of a Nine-Gene Signature Related to Tumor Microenvironment in Lung Adenocarcinoma |
title_short |
Comprehensive Analysis of a Nine-Gene Signature Related to Tumor Microenvironment in Lung Adenocarcinoma |
title_full |
Comprehensive Analysis of a Nine-Gene Signature Related to Tumor Microenvironment in Lung Adenocarcinoma |
title_fullStr |
Comprehensive Analysis of a Nine-Gene Signature Related to Tumor Microenvironment in Lung Adenocarcinoma |
title_full_unstemmed |
Comprehensive Analysis of a Nine-Gene Signature Related to Tumor Microenvironment in Lung Adenocarcinoma |
title_sort |
comprehensive analysis of a nine-gene signature related to tumor microenvironment in lung adenocarcinoma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-09-01 |
description |
Lung adenocarcinoma (LUAD) is the most common malignancy, leading to more than 1 million related deaths each year. Due to low long-term survival rates, the exploration of molecular mechanisms underlying LUAD progression and novel prognostic predictors is urgently needed to improve LUAD treatment. In our study, cancer-specific differentially expressed genes (DEGs) were identified using the robust rank aggregation (RRA) method between tumor and normal tissues from six Gene Expression Omnibus databases (GSE43458, GSE62949, GSE68465, GSE115002, GSE116959, and GSE118370), followed by a selection of prognostic modules using weighted gene co-expression network analysis. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were applied to identify nine hub genes (CBFA2T3, CR2, SEL1L3, TM6SF1, TSPAN32, ITGA6, MAPK11, RASA3, and TLR6) that constructed a prognostic risk model. The RNA expressions of nine hub genes were validated in tumor and normal tissues by RNA-sequencing and single-cell RNA-sequencing, while immunohistochemistry staining from the Human Protein Atlas database showed consistent results in the protein levels. The risk model revealed that high-risk patients were associated with poor prognoses, including advanced stages and low survival rates. Furthermore, a multivariate Cox regression analysis suggested that the prognostic risk model could be an independent prognostic factor for LUAD patients. A nomogram that incorporated the signature and clinical features was additionally built for prognostic prediction. Moreover, the levels of hub genes were related to immune cell infiltration in LUAD microenvironments. A CMap analysis identified 13 small molecule drugs as potential agents based on the risk model for LUAD treatment. Thus, we identified a prognostic risk model including CBFA2T3, CR2, SEL1L3, TM6SF1, TSPAN32, ITGA6, MAPK11, RASA3, and TLR6 as novel biomarkers and validated their prognostic and predicted values for LUAD. |
topic |
tumor microenvironment lung adenocarcinoma biomarker diagnosis prognosis |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.700607/full |
work_keys_str_mv |
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