TY - JOUR
T1 - Effects of nucleic acid metabolism on prognosis and immune invasion of triple-negative breast cancer
AU - Yang, Fan
AU - Dong, Yin
AU - Wu, Siqi
AU - You, Yanting
AU - Yang, Ying
AU - Kong, Jingwei
AU - Chen, Jie
AU - Chen, Liqian
AU - Jiang, Xuefeng
AU - Kwan, Hiu Yee
AU - Zhao, Xiaoshan
AU - Wang, Ji
AU - Liu, Yanyan
N1 - This work was supported by the National Natural Science Foundation of China (Nos.82474527 and 82074289), the Major scientific and technological project of Guangzhou Municipal Health Commission [No. 20252D003], Postdoctoral Science Foundation of China (2022M711536), Postdoctoral Innovation Program of Shandong Province (SDCX-ZG-202501030), the Natural Science Foundation of Guangdong Province of China (2021A1515010673, 2023A1515011078), Traditional Chinese Medicine Administration Project of Guangdong Province of China (20221438), Medical Scientific Research Foundation of Guangdong Province of China (A2021103), Science and Technology Program of Yangjiang of China (SF2021049, SF2022001) and the Scientific Research Fund of Yangiang People’s Hospital of China (G2021003, G2021004). The authors have declared that no competing interest exists. We would like to express our gratitude to the authors of three datasets: TCGA, GSE25055, and GSE25065.
Publisher copyright:
© 2025. The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2025/11/6
Y1 - 2025/11/6
N2 - The nucleic acid metabolism process is driven by various carcinogenic factors, providing a material basis and energy guarantee for the malignant phenotype of tumor cells. However, the role of nucleic acid metabolism in triple-negative breast cancer (TNBC) development remains unclear. Here, we examined the expression patterns of nucleic acid metabolism-related genes (NAMRGs) in the transcriptome of 297 TNBC samples derived from three datasets. We used single-cell RNA sequencing analysis and both in vivo and in vitro experiments to verify the correlation between NAMRGs and tumor metastasis and tumor immune matrix microenvironment (TME) characteristics. According to the results, two different molecular subtypes were identified, and the relationships between the molecular subtypes, four genetic subtypes, and four pathological subtypes were established. Changes in nucleic acid metabolism were related to changes in homologous recombination repair defects (HRD), cell infiltration in the TME, and patient prognosis. We also constructed a prediction model, NAM_model, by including four NAMRGs (DPYD, PDE6G, PDE8B, and TYMS) and integrating it with other clinical indicators. This model was a highly accurate prognostic nomogram, which showed that the prognosis of high-risk patients was poor, with NAMRGs associated with TME immune exhaustion. In addition, NAMRGs were significantly correlated with drug sensitivity to chemotherapy and targeted therapy. In vivo and in vitro studies have shown that PDE8B is an oncogene that promotes tumor growth and induces TNBC metastasis by promoting epithelial-mesenchymal transition (EMT), which has not been reported previously. Single-cell RNA sequencing also revealed the unique effects of nucleic acid metabolism and HRD on exhausted CD8+ T cells. A comprehensive analysis of NAMRGs revealed the potential impact of nucleic acid metabolism-mediated mechanisms, such as HRD and EMT, on the clinical pathological characteristics, TME characteristics, and prognosis of patients with TNBC. These findings have deepened our understanding of the roles of NAMRGs in TNBC and immunotherapy, which will greatly contribute to patient stratification management and individualized clinical decision-making.
AB - The nucleic acid metabolism process is driven by various carcinogenic factors, providing a material basis and energy guarantee for the malignant phenotype of tumor cells. However, the role of nucleic acid metabolism in triple-negative breast cancer (TNBC) development remains unclear. Here, we examined the expression patterns of nucleic acid metabolism-related genes (NAMRGs) in the transcriptome of 297 TNBC samples derived from three datasets. We used single-cell RNA sequencing analysis and both in vivo and in vitro experiments to verify the correlation between NAMRGs and tumor metastasis and tumor immune matrix microenvironment (TME) characteristics. According to the results, two different molecular subtypes were identified, and the relationships between the molecular subtypes, four genetic subtypes, and four pathological subtypes were established. Changes in nucleic acid metabolism were related to changes in homologous recombination repair defects (HRD), cell infiltration in the TME, and patient prognosis. We also constructed a prediction model, NAM_model, by including four NAMRGs (DPYD, PDE6G, PDE8B, and TYMS) and integrating it with other clinical indicators. This model was a highly accurate prognostic nomogram, which showed that the prognosis of high-risk patients was poor, with NAMRGs associated with TME immune exhaustion. In addition, NAMRGs were significantly correlated with drug sensitivity to chemotherapy and targeted therapy. In vivo and in vitro studies have shown that PDE8B is an oncogene that promotes tumor growth and induces TNBC metastasis by promoting epithelial-mesenchymal transition (EMT), which has not been reported previously. Single-cell RNA sequencing also revealed the unique effects of nucleic acid metabolism and HRD on exhausted CD8+ T cells. A comprehensive analysis of NAMRGs revealed the potential impact of nucleic acid metabolism-mediated mechanisms, such as HRD and EMT, on the clinical pathological characteristics, TME characteristics, and prognosis of patients with TNBC. These findings have deepened our understanding of the roles of NAMRGs in TNBC and immunotherapy, which will greatly contribute to patient stratification management and individualized clinical decision-making.
UR - https://www.scopus.com/pages/publications/105021102066
U2 - 10.1038/s41435-025-00366-y
DO - 10.1038/s41435-025-00366-y
M3 - Journal article
C2 - 41198929
SN - 1466-4879
JO - Genes and Immunity
JF - Genes and Immunity
ER -
