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

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 (ERR alpha) 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 ERR alpha in lung cancer and to provide a novel perspective for lung cancer early diagnosis, targeted therapy, and prognosis assessment. Methods: The correlation between ERR alpha 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 ERR alpha in tumor tissues. ERR alpha-knockdown LUAD cells were generated and the impacts of ERR alpha on cell proliferation, invasion, and metastasis were further analyzed. Cancerous and paracancerous tissues were collected to semi-quantitative the levels of ERR alpha in LUAD clinical samples (n=88), combined with clinical information for prognostic analysis. Results: The KM plotter analysis suggested that ERR alpha is correlated with poor prognosis in LUAD (n=720) rather than in lung squamous cell carcinoma (LSCC) (n=524). ERR alpha is also upregulated in tumor tissues obtained from LUAD model mice. Quantitative analysis suggested an abnormal elevation of ERR alpha in LUAD cells rather than in LSCC cells. The results demonstrated that downregulation of ERR alpha impairs proliferation, invasion and migration abilities (P<0.01). The prognostic analysis showed that the overexpressed ERR alpha in LUAD was positively correlated with low survival rates (HR=1.597). The results indicate that the death risk of ERR alpha high expression is 1.597 times higher than ERR alpha low level in LUAD patients. Conclusion: In summary, our findings suggest that ERR alpha is a potential aggressive factor of LUAD which implies poor prognosis.