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ERRα is an aggressive factor in lung adenocarcinoma indicating poor prognostic outcomes

Authors Li P, Wang J, Wu D, Ren X, Wu W, Zuo R, Zeng Q, Wang B, He X, Yuan J, Xie N

Received 10 February 2019

Accepted for publication 28 July 2019

Published 2 September 2019 Volume 2019:11 Pages 8111—8123

DOI https://doi.org/10.2147/CMAR.S204732

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Ping Li,1–3,* Jian Wang,4,* Desheng Wu,3 Xiaohu Ren,3 Wen Wu,2,3 Ran Zuo,2 Qingbo Zeng,3 Bingyu Wang,2 Xi He,1 Jianhui Yuan,2,5 Ni Xie1,2

1Biobank, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, People’s Republic of China; 2Department of Medicine, University of South China, Hengyang 421001, People’s Republic of China; 3Department of Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen 518035, People’s Republic of China; 4Department of Thoracic Surgery, The Shenzhen People’s Hospital, Shenzhen 518020, People’s Republic of China; 5Department of Occupational Health, Shenzhen Nanshan District Center for Disease Control and Prevention, Shenzhen 518054, People’s Republic of China

Correspondence: Ni Xie
Biobank Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, No. 3002 Sungang West Road, Futian District, Shenzhen 518035, People’s Republic of China
Tel +86 1 350 158 0802
Fax +86 7 558 300 3435
Email xn100@szu.edu.cn

Jianhui Yuan
Department of Occupational Health, Shenzhen Nanshan District Center for Disease Control and Prevention, No. 95 Nanshang Road, Nanshan District, Shenzhen 518054, People’s Republic of China
Tel +86 1 350 158 0509
Fax +86 7 558 300 3435
Email jianhui_yuan@126.com

*These authors contributed equally to this work

Purpose: Lung cancer is one of the most life-threatening cancer worldwide with poor prognosis attributed to the lack of early diagnosis and proper therapy. The estrogen-related receptor alpha (ERRα) is a multifunctional protein not limited to bind ligands and has been reported to be associated with numerous cancers. This study aimed to investigate the potential role of ERRα in lung cancer and to provide a novel perspective for lung cancer early diagnosis, targeted therapy, and prognosis assessment.
Methods: The correlation between ERRα mRNA expression and survival time of the online clinical data about lung cancer was analyzed by using Kaplan–Meier (KM) plotter. A mouse model of lung adenocarcinoma (LUAD) was constructed to detect the expression level of ERRα in tumor tissues. ERRα-knockdown LUAD cells were generated and the impacts of ERRα on cell proliferation, invasion, and metastasis were further analyzed. Cancerous and paracancerous tissues were collected to semi-quantitative the levels of ERRα in LUAD clinical samples (n=88), combined with clinical information for prognostic analysis.
Results: The KM plotter analysis suggested that ERRα is correlated with poor prognosis in LUAD (n=720) rather than in lung squamous cell carcinoma (LSCC) (n=524). ERRα is also upregulated in tumor tissues obtained from LUAD model mice. Quantitative analysis suggested an abnormal elevation of ERRα in LUAD cells rather than in LSCC cells. The results demonstrated that downregulation of ERRα impairs proliferation, invasion and migration abilities (P<0.01). The prognostic analysis showed that the overexpressed ERRα in LUAD was positively correlated with low survival rates (HR=1.597). The results indicate that the death risk of ERRα high expression is 1.597 times higher than ERRα low level in LUAD patients.
Conclusion: In summary, our findings suggest that ERRα is a potential aggressive factor of LUAD which implies poor prognosis.

Keywords: lung adenocarcinoma, ERRα, estrogen-related receptor alpha, proliferation, migration, metastasis, poor prognosis

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