The prognostic value and immune regulatory role of BRF1 in pan-cancer, and its function in esophageal squamous cell carcinoma_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

XU Jianxin ¹ , LI Zihao ² , LÜ Wang ² , XU Zhiyang ¹ , YI Yunfeng ³ , CHEN Songlin ³ ,  HU Jian ² ,  WANG Luming ²

1. Department of Thoracic and Cardiac Surgery, The First Hospital of Putian City, Clinical Medical Department of Fujian Medical University, Putian, 351100, Fujian, , P. R. China;
2. Department of Thoracic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310003, P. R. China;
3. 909 Hospital of the Joint Service Support Force of the Chinese People's Liberation Army, Zhangzhou, 363000, Fujian, P. R. China S1Jianxin and LI Zihao are the co-first authors;

Corresponding author：

HU Jian, Email: dr_hujian@zju.edu.cn; WANG Luming, Email: 1507144@zju.edu.cn

Keywords：

BRF1; pan-cancer analysis; esophageal squamous cell carcinoma; ferroptosis; gene co-expression; immunomodulation

DOI：

10.7507/1007-4848.202505063

Video：

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Objective To investigate the pan-cancer expression profile, prognostic value, co-expression networks, immune regulatory roles of BRF1, and its biological functions and molecular mechanisms in esophageal squamous cell carcinoma (ESCC). Methods Integrated analysis of TCGA pan-cancer datasets was performed to evaluate BRF1 expression differences between tumor/normal tissues, survival correlations, co-expressed gene-enriched pathways, and immune features (immune checkpoints, cytokines, immune cell infiltration). GEO datasets were used to validate BRF1 expression in ESCC. BRF1 was knocked down using siRNA in ESCC cells, with MTT and Transwell assays assessing proliferation/migration, and Western blot analyzing proliferation- (PCNA) and migration-related proteins (Vimentin, MMP, E-Cadherin). TCGA data were analyzed to explore BRF1-ferroptosis correlations. Results BRF1 was significantly upregulated in over 20 cancer types. High BRF1 expression predicted poor prognosis in adrenocortical carcinoma (ACC) and prostate adenocarcinoma (PRAD). BRF1 positively regulated T cell-mediated cell death pathways in ESCA and circadian rhythm pathways in PAAD. BRF1 exhibited cancer-type-specific correlations with immune checkpoints, cytokine networks, and immune cell infiltration. In vitro, BRF1 knockdown suppressed ESCC proliferation (PCNA downregulation) and migration (Vimentin/MMP downregulation, E-Cadherin upregulation). BRF1 expression positively correlated with ferroptosis antagonists (GPX4, HSPA5, SLC7A11). Conclusion BRF1 demonstrates complex pan-cancer expression and functional heterogeneity, modulating tumor progression and immune infiltration. BRF1 promotes ESCC proliferation and migration, potentially via ferroptosis resistance regulation, highlighting its potential as a therapeutic target in ESCC.

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1. Goodfellow SJ, Innes F, Derblay LE, et al. Regulation of RNA polymerase Ⅲ transcription during hypertrophic growth. EMBO J, 2006, 25(7): 1522-1533.
2. Enserink JM, Chymkowitch P. Cell cycle-dependent transcription: the cyclin dependent kinase Cdk1 is a direct regulator of basal transcription machineries. Int J Mol Sci, 2022, 23(3): 1293.
3. Uemura M, Zheng Q, Koh CM, et al. Overexpression of ribosomal RNA in prostate cancer is common but not linked to rDNA promoter hypomethylation. Oncogene, 2012, 31(10): 1254-1263.
4. Täuber H, Hüttelmaier S, Köhn M. POLIII-derived non-coding RNAs acting as scaffolds and decoys. J Mol Cell Biol, 2019, 11(10): 880-885.
5. Xu Y, Yu C, Zhang H, et al. Downregulation of Brf1 induces liver failure and inhibits hepatocellular carcinoma progression by promoting apoptosis. J Cancer, 2024, 15(17): 5577-5593.
6. Fang Z, Yi Y, Shi G, et al. Role of Brf1 interaction with ERα, and significance of its overexpression, in human breast cancer. Mol Oncol, 2017, 11(12): 1752-1767.
7. Zhang Y, Wu H, Yang F, et al. Prognostic value of the expression of DNA repair-related biomarkers mediated by alcohol in gastric cancer patients. Am J Pathol, 2018, 188(2): 367-377.
8. Loveridge CJ, Slater S, Campbell KJ, et al. BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration. Oncogene, 2020, 39(8): 1797-1806.
9. Yang H, Wang F, Hallemeier CL, et al. Oesophageal cancer. Lancet, 2024, 404(10466): 1991-2005.
10. Asanuma K, Iijima K, Shimosegawa T. Gender difference in gastro-esophageal reflux diseases. World J Gastroenterol, 2016, 22(5): 1800-1810.
11. Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov, 2022, 12(1): 31-46.
12. Zhu H, Ma X, Ye T, et al. Esophageal cancer in China: practice and research in the new era. Int J Cancer, 2023, 152(9): 1741-1751.
13. Liko D, Mitchell L, Campbell KJ, et al. Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas. Cell Death Differ, 2019, 26(12): 2535-2550.
14. Weeden CE, Hill W, Lim EL, et al. Impact of risk factors on early cancer evolution. Cell, 2023, 186(8): 1541-1563.
15. Crosby D, Bhatia S, Brindle KM, et al. Early detection of cancer. Science, 2022, 375(6586): eaay9040.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

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