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 ^1,2 , LI Zihao ³ , Lü Wang ³ , XU Zhiyang ^1,2 , YI Yunfeng ⁴ , CHEN Songlin ⁴ ,  HU Jian ³ ,  WANG Luming ³

1. Department of Thoracic and Cardiovascular Surgery, The First Hospital of Putian, Putian, 351100, Fujian, P. R. China;
2. Graduate School of Fujian Medical University, Fuzhou, 350122, P. R. China;
3. Department of General Thoracic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310003, P. R. China;
4. The 909th Hospital of the Joint Logistic Support Force of the Chinese People's Liberation Army, Zhangzhou, 363005, Fujian, P. R. China;

Corresponding?author：

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

Keywords：

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

DOI：

10.7507/1007-4848.202505063

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the expression profile, prognostic value, gene co-expression network, and immunomodulatory role of BRF1 in a pan-cancer context, and to explore its biological functions and molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC). Methods The pan-cancer dataset from The Cancer Genome Atlas (TCGA) was utilized to analyze the differential expression of BRF1 in tumor versus normal tissues, its association with patient survival, pathway enrichment for co-expressed genes, and immune features (including immune checkpoints, cytokines, and immune cell infiltration). The expression profile of BRF1 in ESCC was validated using the Gene Expression Omnibus (GEO) database. In vitro, BRF1 was knocked down in ESCC cells using siRNA. Cell proliferation and migration were assessed by MTT and Transwell assays, respectively. The expression levels of proliferation- and migration-related proteins were detected by Western blotting. The correlation between BRF1 and ferroptosis was analyzed using TCGA data. Results BRF1 was significantly upregulated in over 20 types of cancer, and its high expression was associated with poor prognosis in patients with adrenocortical carcinoma and prostate adenocarcinoma. BRF1 was found to positively regulate the T-cell-mediated cell death pathway in esophageal adenocarcinoma and was associated with the circadian rhythm regulation pathway in pancreatic adenocarcinoma. The correlation of BRF1 with immune checkpoints, cytokine networks, and immune cell infiltration was found to be cancer type-specific. In vitro experiments demonstrated that knocking down BRF1 significantly inhibited the proliferation of ESCC cells, accompanied by the downregulation of the proliferation marker PCNA. Cell migration was also significantly impaired, with decreased expression of Vimentin and MMPs and increased expression of E-cadherin. Furthermore, the expression of BRF1 was positively correlated with that of ferroptosis-antagonizing genes, such as GPX4, HSPA5, and SLC7A11. Conclusion BRF1 plays complex roles in pan-cancer, participating in the regulation of tumorigenesis, progression, and immune infiltration. BRF1 promotes the proliferation and migration of ESCC cells, a mechanism potentially associated with the regulation of ferroptosis resistance. These findings suggest that BRF1 could be a potential therapeutic target for ESCC.

Citation： XU Jianxin, LI Zihao, Lü Wang, XU Zhiyang, YI Yunfeng, CHEN Songlin, HU Jian, WANG Luming. 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, 2026, 33(1): 122-131. doi: 10.7507/1007-4848.202505063 Copy

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.	T?uber H, Hüttelmaier S, K?hn 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.

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. T?uber H, Hüttelmaier S, K?hn 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

The prognostic value and immune regulatory role of BRF1 in pan-cancer, and its function in esophageal squamous cell carcinoma

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content