Association between taurine transporter SLC6A6 and breast cancer development and prognosis: a Mendelian randomization analysis

Abstract Background Breast cancer is the most common malignancy among women worldwide, with early screening and diagnosis being crucial for improving patient prognosis. Taurine, as an important metabolite, shows significant changes during breast cancer development, while the taurine transporter SLC6...

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Main Authors: Xinping Huang, Hailong Shu, Man Xu, Weixiao Ke, Wanting Chen, Wenbin Huang, Hai Wang, Yifan Zhu, Yongxia Yang
Format: Article
Language:English
Published: Springer 2025-07-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-03246-z
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author Xinping Huang
Hailong Shu
Man Xu
Weixiao Ke
Wanting Chen
Wenbin Huang
Hai Wang
Yifan Zhu
Yongxia Yang
author_facet Xinping Huang
Hailong Shu
Man Xu
Weixiao Ke
Wanting Chen
Wenbin Huang
Hai Wang
Yifan Zhu
Yongxia Yang
author_sort Xinping Huang
collection DOAJ
description Abstract Background Breast cancer is the most common malignancy among women worldwide, with early screening and diagnosis being crucial for improving patient prognosis. Taurine, as an important metabolite, shows significant changes during breast cancer development, while the taurine transporter SLC6A6 may play a key role in breast cancer progression. Methods This study systematically investigated the relationship between taurine level changes and breast cancer development through cell experiments, animal models, and clinical sample analysis. 1H NMR and HPLC techniques were used to measure taurine levels in different breast cancer cell lines, MMTV-PyMT transgenic mouse models, and clinical patient serum. Molecular docking, functional analysis, and immune infiltration analysis were employed to explore the mechanism of SLC6A6. Mendelian randomization (MR) analysis was used to evaluate the causal relationship between immune cell subsets and breast cancer risk. Results Intracellular taurine levels were elevated, while extracellular taurine levels decreased in breast cancer cells, correlating with malignancy degree. Serum taurine levels in MMTV-PyMT mice and clinical patients decreased continuously with disease progression, with significant changes detectable at the carcinoma in situ stage. Serum taurine demonstrated good diagnostic value as an early breast cancer marker, with ROC analysis showing an AUC of 0.939, sensitivity of 0.900, and specificity of 1.000 in distinguishing benign tumors from carcinoma in situ. SLC6A6 was highly expressed in breast cancer tissues and significantly associated with poor patient prognosis. Mendelian randomization analysis revealed potential causal relationships between specific immune cell subsets (such as naive B cells, TCRgd cells) and breast cancer risk, while CD14+CD16− monocytes showed a protective effect. Single-cell sequencing analysis indicated that SLC6A6 is primarily enriched in endothelial cells and fibroblasts within tumor tissues. Conclusion Taurine metabolic reprogramming can serve as a potential marker for early breast cancer diagnosis. SLC6A6 participates in breast cancer progression by regulating taurine levels and influencing immune infiltration, representing an independent predictor of breast cancer prognosis and a potential therapeutic target.
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spelling doaj-art-a0b0582a49d74c7a8b0f7efe2fdeb5fb2025-08-20T03:46:15ZengSpringerDiscover Oncology2730-60112025-07-0116112310.1007/s12672-025-03246-zAssociation between taurine transporter SLC6A6 and breast cancer development and prognosis: a Mendelian randomization analysisXinping Huang0Hailong Shu1Man Xu2Weixiao Ke3Wanting Chen4Wenbin Huang5Hai Wang6Yifan Zhu7Yongxia Yang8College of Basic Medicine, Guangdong Pharmaceutical UniversityCollege of Medical Information Engineering, Guangdong Pharmaceutical UniversityCollege of Basic Medicine, Guangdong Pharmaceutical UniversityCollege of Medical Information Engineering, Guangdong Pharmaceutical UniversityCollege of Pharmacy, Guangdong Pharmaceutical UniversityDepartment of Breast Care Surgery, The First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuang Zhou Ch-Rui Health Scientific., LtdDepartment of Thyroid Surgery, The First Affiliated Hospital of Sun Yat-Sen UniversityCollege of Medical Information Engineering, Guangdong Pharmaceutical UniversityAbstract Background Breast cancer is the most common malignancy among women worldwide, with early screening and diagnosis being crucial for improving patient prognosis. Taurine, as an important metabolite, shows significant changes during breast cancer development, while the taurine transporter SLC6A6 may play a key role in breast cancer progression. Methods This study systematically investigated the relationship between taurine level changes and breast cancer development through cell experiments, animal models, and clinical sample analysis. 1H NMR and HPLC techniques were used to measure taurine levels in different breast cancer cell lines, MMTV-PyMT transgenic mouse models, and clinical patient serum. Molecular docking, functional analysis, and immune infiltration analysis were employed to explore the mechanism of SLC6A6. Mendelian randomization (MR) analysis was used to evaluate the causal relationship between immune cell subsets and breast cancer risk. Results Intracellular taurine levels were elevated, while extracellular taurine levels decreased in breast cancer cells, correlating with malignancy degree. Serum taurine levels in MMTV-PyMT mice and clinical patients decreased continuously with disease progression, with significant changes detectable at the carcinoma in situ stage. Serum taurine demonstrated good diagnostic value as an early breast cancer marker, with ROC analysis showing an AUC of 0.939, sensitivity of 0.900, and specificity of 1.000 in distinguishing benign tumors from carcinoma in situ. SLC6A6 was highly expressed in breast cancer tissues and significantly associated with poor patient prognosis. Mendelian randomization analysis revealed potential causal relationships between specific immune cell subsets (such as naive B cells, TCRgd cells) and breast cancer risk, while CD14+CD16− monocytes showed a protective effect. Single-cell sequencing analysis indicated that SLC6A6 is primarily enriched in endothelial cells and fibroblasts within tumor tissues. Conclusion Taurine metabolic reprogramming can serve as a potential marker for early breast cancer diagnosis. SLC6A6 participates in breast cancer progression by regulating taurine levels and influencing immune infiltration, representing an independent predictor of breast cancer prognosis and a potential therapeutic target.https://doi.org/10.1007/s12672-025-03246-zBreast cancerTaurineSLC6A6Metabolic markerEarly diagnosisImmune infiltration
spellingShingle Xinping Huang
Hailong Shu
Man Xu
Weixiao Ke
Wanting Chen
Wenbin Huang
Hai Wang
Yifan Zhu
Yongxia Yang
Association between taurine transporter SLC6A6 and breast cancer development and prognosis: a Mendelian randomization analysis
Discover Oncology
Breast cancer
Taurine
SLC6A6
Metabolic marker
Early diagnosis
Immune infiltration
title Association between taurine transporter SLC6A6 and breast cancer development and prognosis: a Mendelian randomization analysis
title_full Association between taurine transporter SLC6A6 and breast cancer development and prognosis: a Mendelian randomization analysis
title_fullStr Association between taurine transporter SLC6A6 and breast cancer development and prognosis: a Mendelian randomization analysis
title_full_unstemmed Association between taurine transporter SLC6A6 and breast cancer development and prognosis: a Mendelian randomization analysis
title_short Association between taurine transporter SLC6A6 and breast cancer development and prognosis: a Mendelian randomization analysis
title_sort association between taurine transporter slc6a6 and breast cancer development and prognosis a mendelian randomization analysis
topic Breast cancer
Taurine
SLC6A6
Metabolic marker
Early diagnosis
Immune infiltration
url https://doi.org/10.1007/s12672-025-03246-z
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