FGL1 - a novel biomarker and target for non-small cell lung cancer - promoting tumor progression and metastasis through KDM4A/STAT3 transcription mechanism

Sep 21, 2026

Uploaded by Oliver

Non-small cell lung cancer (NSCLC) remains common worldwide with poor prognosis, requiring deeper insight into its pathogenesis and discovery of actionable therapeutic targets. This study identifies fibrinogen-like protein 1 (FGL1) as a driver of NSCLC cell proliferation, migration, and invasion. Mechanistically, STAT3 functions as a transcription factor recruited to the FGL1 promoter, while KDM4A enhances STAT3-dependent transcription by removing H3K9me3. FGL1 is elevated in tumor tissues and correlates with worse overall survival. Dynamic decreases of FGL1 on circulating tumor cells predict better therapeutic responses, supporting FGL1 as a potential biomarker and target.

LanguageEnglish

CategoryResearch & Report

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Liu et al. J Exp Clin Cancer Res (2024) 43:213 [https://doi.org/10.1186/s13046-024-03140-6](https://doi.org/10.1186/s13046-024-03140-6) Journal of Experimental & Clinical Cancer Research RESEARCH Open Access FGL1: a novel biomarker and target for non-small cell lung cancer, promoting tumor progression and metastasis through KDM4A/ STAT3 transcription mechanism Tian Yao Liu1†, Jin Shan Yan1†, Xin Li1†, Lu Xu1†, Jun Li Hao1, Su Ya Zhao1, Qi Lin Hu1, Fang Jian Na2, He Ming Li 1,3* , Yue Zhao4* and Ming Fang Zhao1* Abstract Non-small cell lung cancer (NSCLC) is characterized by a high incidence rate and poor prognosis worldwide. A deeper insight into the pathogenesis of NSCLC and identification of novel therapeutic targets are essential to improve the prognosis of NSCLC. In this study, we revealed that fibrinogen-like protein 1 (FGL1) promotes proliferation, migration, and invasion of NSCLC cells. Mechanistically, we found that Stat3 acts as a transcription factor and can be recruited to the FGL1 promoter, enhancing FGL1 promoter activity. Lysine-specific demethylase 4A (KDM4A) interacts with Stat3 and facilitates the removal of methyl groups from H3K9me3, thereby enhancing Stat3-mediated transcription of FGL1 . Furthermore, we observed that Stat3 and KDM4A promote NSCLC cell proliferation, migration, and invasion partly by upregulating FGL1 expression. Additionally, the expression of FGL1 was significantly higher in cancer tissues (n= 90) than in adjacent non-cancerous tissues (n = 90) . Furthermore, patients with high FGL1 expression had a shorter overall survival (OS) compared to those with low FGL1 expression. We measured the expression levels of FGL1 on circulating tumor cells (CTCs) in 65 patients and found that patients with a dynamic decrease in FGL1 expression on CTCs exhibited a better therapeutic response. These findings suggest that the dynamic changes in FGL1 expression can serve as a potential biomarker for predicting treatment efficacy in NSCLC. Overall, this study revealed the significant role and regulatory mechanisms of FGL1 in the development of NSCLC, suggesting its potential as a therapeutic target for patients with NSCLC. Future studies should provide more personalized and effective treatment options for patients with NSCLC to improve clinical outcomes. Keywords FGL1, KDM4A, Stat3, NSCLC, Transcriptional regulation †Tian Yao Liu, Jin Shan Yan, Xin Li and Lu Xu contributed equally to this work. *Correspondence: He Ming Li[liheming8563@hotmail.com](liheming8563@hotmail.com)[ ](liheming8563@hotmail.com)Yue Zhao [yzhao30@cmu.edu.cn](yzhao30@cmu.edu.cn)[ ](yzhao30@cmu.edu.cn)Ming Fang Zhao [zhaomf618@126.com](zhaomf618@126.com) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[http://creativecom](http://creativecom)[mons.org/publicdomain/zero/1.0/](mons.o

FAQs

What role does FGL1 play in non-small cell lung cancer (NSCLC)?

FGL1 promotes NSCLC cell proliferation, migration, and invasion. Its expression is higher in cancer tissues than in adjacent non-cancer tissues and is associated with poorer overall survival.

How do STAT3 and KDM4A regulate FGL1 expression?

STAT3 acts as a transcription factor recruited to the FGL1 promoter to enhance promoter activity. KDM4A interacts with STAT3 and facilitates removal of methyl groups from H3K9me3, thereby enhancing STAT3-mediated transcription of FGL1.

Why is FGL1 considered a biomarker for predicting treatment response?

Patients showing a dynamic decrease in FGL1 expression on circulating tumor cells (CTCs) had a better therapeutic response. These findings suggest that changing FGL1 levels may help predict treatment efficacy in NSCLC.

Sep 21, 2026

Uploaded by Oliver