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Plasma THBS1 as a predictive biomarker for poor prognosis and brain metastasis in patients with HER2-enriched breast cancer

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Abstract

Background

Thrombospondin-1 (THBS1) is a secretory adhesive glycoprotein involved in the progression of multiple malignancies, including breast cancer. However, the clinical significance and prognostic role of plasma THBS1 in breast cancer have yet to be clarified.

Methods

Plasma THBS1 levels in 627 breast cancer patients were analyzed by enzyme-linked immunosorbent assay. Bone marrow blood was drawn from the anterior/posterior superior iliac spine to detect the presence of disseminated tumor cells (DTCs). The effects of plasma THBS1 on the clinicopathological characteristics and survival prediction of breast cancer patients were explored.

Results

Plasma THBS1 did not correlate with overall survival, breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) in the entire breast cancer cohort. Notably, HER2-enriched patients with high-plasma THBS1 levels had significantly shorter BCSS (P = 0.027) and DDFS (P = 0.011) than those with low levels. Multivariate analyses revealed that plasma THBS1 was an independent prognostic marker of BCSS (P = 0.026) and DDFS (P = 0.007) in HER2-enriched patients. THBS1 levels were 24% higher in positive DTC patients than in negative DTC patients (P = 0.031), and high levels were significantly associated with poor BCSS in positive DTC patients (HR 2.08, 95% CI 1.17–3.71; P = 0.019). Moreover, high-plasma THBS1 levels were specifically associated with an increased occurrence of brain metastasis in HER2-enriched patients (P = 0.041).

Conclusion

These findings suggest that plasma THBS1 may be serving as an unfavorable prognosis predictor for HER2-enriched breast cancer and justifies the need for further research.

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Acknowledgements

We sincerely thank the breast cancer patients who participated in this study.

Funding

This work was supported by the National Natural Science Foundation of China (82103630).

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Authors and Affiliations

  1. Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, China

    Yang Li, Jun Qin, Guiming Chen, Weidong Wu & Xing Sun

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  1. Yang Li
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  2. Jun Qin
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  3. Guiming Chen
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  4. Weidong Wu
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  5. Xing Sun
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Contributions

YL: Conceptualization, Investigation, Methodology, Software, Validation, Resources, Funding acquisition, Writing (original draft, review, and editing). JQ: Conceptualization, Software, Resources, Validation. GC: Project administration, Visualization, Supervision, Investigation. WW: Conceptualization, Validation, Resources, Project administration, Formal analysis. XS: Conceptualization, Validation, Data curation, Visualization, Supervision, Project administration, Writing (review and editing).

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Correspondence to Xing Sun.

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In the studies, all procedures involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and in conformity with the 1964 Helsinki declaration, in addition to its later amendments or comparable ethical standards. No animal experiment was involved in the current study. The research protocol was reviewed and authorized by the Ethics Committee of the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine. Informed consent was obtained from each participant.

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10147_2024_2472_MOESM1_ESM.tif

Fig. S1. The cBioPortal database was used to perform co-expression analysis of THBS1 and potential molecules on the basis of the mRNA expression (http://cbioportal.org/). The mRNA expression levels of THBS1 in breast cancer patients are found to be positively correlated with the expression of PIK3CA, TGFB1, MAPK14, STAT3, TNFRSF1A, and EGR1 (TIF 26208 KB)

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Li, Y., Qin, J., Chen, G. et al. Plasma THBS1 as a predictive biomarker for poor prognosis and brain metastasis in patients with HER2-enriched breast cancer. Int J Clin Oncol 29, 427–441 (2024). https://doi.org/10.1007/s10147-024-02472-9

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  • DOI: https://doi.org/10.1007/s10147-024-02472-9

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