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

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 Xie1,21Biobank, 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 ChinaCorrespondence: Ni XieBiobank Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, No. 3002 Sungang West Road, Futian District, Shenzhen 518035, People’s Republic of ChinaTel +86 1 350 158 0802Fax +86 7 558 300 3435Email xn100@szu.edu.cnJianhui YuanDepartment of Occupational Health, Shenzhen Nanshan District Center for Disease Control and Prevention, No. 95 Nanshang Road, Nanshan District, Shenzhen 518054, People’s Republic of ChinaTel +86 1 350 158 0509Fax +86 7 558 300 3435Email jianhui_yuan@126.com*These authors contributed equally to this workPurpose: 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