ERRα is an Aggressive Factor in Lung Adenocarcinoma Indicating Poor Prognostic Outcomes

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2019 Oct 1

PMID 31564971

Citations 10

Authors

Ping Li

Jian Wang

Desheng Wu

Xiaohu Ren

Wen Wu

Ran Zuo

Qingbo Zeng

Bingyu Wang

Xi He

Jianhui Yuan

Ni Xie

Affiliations

Soon will be listed here.

Abstract

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 (<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.

Citing Articles

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Association of Irisin/FNDC5 with ERRα and PGC-1α Expression in NSCLC.

Nowinska K, Jablonska K, Ciesielska U, Piotrowska A, Haczkiewicz-Lesniak K, Pawelczyk K Int J Mol Sci. 2022; 23(22).

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Hypercholesterolemia in Cancer and in Anorexia Nervosa: A Hypothesis for a Crosstalk.

Gizzi G, Cataldi S, Mazzeschi C, Delvecchio E, Ceccarini M, Codini M Int J Mol Sci. 2022; 23(13).

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Cholesterol promotes EGFR-TKIs resistance in NSCLC by inducing EGFR/Src/Erk/SP1 signaling-mediated ERRα re-expression.

Pan Z, Wang K, Wang X, Jia Z, Yang Y, Duan Y Mol Cancer. 2022; 21(1):77.

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Targeting Estrogens and Various Estrogen-Related Receptors against Non-Small Cell Lung Cancers: A Perspective.

Maitra R, Malik P, Mukherjee T Cancers (Basel). 2022; 14(1).

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