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已发表论文
血浆胆汁酸谱分析揭示了儿童脓毒症的新型早期诊断生物标志物
Authors Xu L, Xu H, Jiang D, Song S , Wang G, Zhang X, Zhang Y, Qian J , Kang J, Cai F
Received 12 July 2025
Accepted for publication 7 December 2025
Published 26 December 2025 Volume 2025:17 Pages 1413—1425
DOI https://doi.org/10.2147/BCTT.S549363
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Harikrishna Nakshatri
Lu Xu,* Hongbo Xu,* Dengsheng Jiang,* Shilong Song, Gengming Wang, Xianwen Zhang, Yajun Zhang, Jing Qian, Jia Kang, Feng Cai
Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Feng Cai, Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical University, Zhihuai Road, Bengbu, Anhui, 233000, People’s Republic of China, Tel +86-13645529901, Email caifeng1225@bbmu.edu.cn
Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer lacking estrogen receptor (ER), progesterone receptor (PR), and HER2 expression, which limits targeted therapies. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are known to secrete factors that promote tumor progression. The role of neuregulin-1 (NRG1), a ligand of HER3 and HER4, in TNBC and its association with CAFs remains unclear.
Methods: We analyzed NRG1 mRNA and protein levels in TNBC tumor and adjacent tissues using qRT-PCR and ELISA, and evaluated their relationship with clinicopathological parameters and prognosis in 174 patients. Serum NRG1 levels were assessed via ELISA in TNBC patients and healthy controls. The effects of CAF-secreted NRG1 on TNBC cells were studied using conditioned medium, siRNA knockdown, and xenograft mouse models. Statistical analyses, including ROC curves and survival analyses, were performed to determine diagnostic and prognostic value.
Results: NRG1 expression was significantly upregulated in TNBC tissues and serum compared to controls, correlating with advanced TNM stages and poor prognosis. ROC analysis demonstrated diagnostic value of NRG1 in tissues and serum. CAFs secreted higher levels of NRG1 compared to normal fibroblasts. Conditioned medium from CAFs enhanced TNBC cell proliferation, migration, and MMP9 expression, effects reduced by NRG1 knockdown. In vivo, CAF-conditioned medium promoted tumor growth, while NRG1 knockdown reduced this effect.
Conclusion: Our findings suggest that CAF-secreted NRG1 is closely associated with TNBC progression and may represent a potential biomarker and therapeutic target, although further validation is needed to establish causality.
Keywords: triple-negative breast cancer, NRG1, cancer-associated fibroblasts, tumor microenvironment, biomarker
Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Feng Cai, Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical University, Zhihuai Road, Bengbu, Anhui, 233000, People’s Republic of China, Tel +86-13645529901, Email caifeng1225@bbmu.edu.cn
Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer lacking estrogen receptor (ER), progesterone receptor (PR), and HER2 expression, which limits targeted therapies. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are known to secrete factors that promote tumor progression. The role of neuregulin-1 (NRG1), a ligand of HER3 and HER4, in TNBC and its association with CAFs remains unclear.
Methods: We analyzed NRG1 mRNA and protein levels in TNBC tumor and adjacent tissues using qRT-PCR and ELISA, and evaluated their relationship with clinicopathological parameters and prognosis in 174 patients. Serum NRG1 levels were assessed via ELISA in TNBC patients and healthy controls. The effects of CAF-secreted NRG1 on TNBC cells were studied using conditioned medium, siRNA knockdown, and xenograft mouse models. Statistical analyses, including ROC curves and survival analyses, were performed to determine diagnostic and prognostic value.
Results: NRG1 expression was significantly upregulated in TNBC tissues and serum compared to controls, correlating with advanced TNM stages and poor prognosis. ROC analysis demonstrated diagnostic value of NRG1 in tissues and serum. CAFs secreted higher levels of NRG1 compared to normal fibroblasts. Conditioned medium from CAFs enhanced TNBC cell proliferation, migration, and MMP9 expression, effects reduced by NRG1 knockdown. In vivo, CAF-conditioned medium promoted tumor growth, while NRG1 knockdown reduced this effect.
Conclusion: Our findings suggest that CAF-secreted NRG1 is closely associated with TNBC progression and may represent a potential biomarker and therapeutic target, although further validation is needed to establish causality.
Keywords: triple-negative breast cancer, NRG1, cancer-associated fibroblasts, tumor microenvironment, biomarker