Abstract Introduction. Desmoplakin (DSP) is a membrane subcoat plaque protein, primary co-located within the desmosomes, which are membrane structures found in tissues such as skin and muscles. Known DSP interactive proteins include desomosome cadherin desmogleins (DSG)and desmocollins (DSC). Although an early indication of a possible loss of the DSP protein, particularly in high grade tumours in human breast cancer was reported (Davies et al 1999), the impact of DSP on the clinical course and prognosis in breast cancer has not been fully explored. Here, we investigated the expression of DSP together with the membrane integral demososome protein DSG1 (desmoglein-1), aiming to establish a possible prognostic significance in clinical breast cancer. Methods and Results. The expression of DSP gene transcript was quantitatively evaluated in a cohort of clinical breast cancer with a ten-year followup. The expression levels were fully analysed against the clinical and pathological factors and the long term clinical outcome of the patients. Where appropriate, the prognostic significance was conducted using Kaplan-Meier model and Bayes analyses. The most significant finding was that the expression levels of DSP is linked to the clinical outcome of the patients. Breast tumours which developed distant metastasis, local recurrence and in patients who died from breast cancer exhibited a significant reduction of DSP expression when compared with tumours from those who remained disease free (p=0.036, p=0.020 and p=0.022, respectively, versus disease free). The reduction of DSP was seen profoundly in ER positive tumours and HER2 positive tumours. Survival analysis indicated that DSP expression is a favourable factor for overall survival (OS) with an AUC at 0.241 (p0.0001) and hazard ratio (HR) at 0.063 (95% confidence internal 0.008-0.477, p=0.007 by Cox regression), a connection supported by an impressive Bayes factor (192.1). The connection with OS was observed across the molecular subtypes and when the molecular subtypes and hormone receptor status were considered, DSP remained a significant OS indicator in multivariant analysis. Very similarly, DSP expression is also a favourable indicator for disease free survival (DSF) (p=0.006), again seen in most subtypes. Significant correlation between expression pattern of DSP and DSG1 was not observed. Finally, evidence suggests that DSP expression level is a good indicator for patient response to both neoadjuvant and adjuvant chemotherapies in patients with breast cancer. Conclusion. Desmoplakin exhibits characteristics as a favourable prognostic indicator for patient overall and disease free survival in breast cancer patients. The connection, which is less influenced by the molecular subtypes, also has value in predicting the chemotherapeutic response of the patients. Reference: Davies EL et al. 1999. The immunohistochemical expression of desmoplakin and its role in vivo in the progression and metastasis of breast cancer. Eur J Cancer, 35, 902 Citation Format: H. Y. Xiang, H. Y. Xiang, X. Li, C. Wang, T. A. Martin, E. Davies, K. Mokbel, Y. H. Liu, W. G. Jiang. Desmoplakin, DSP, is a potential tumour suppressive protein in human breast cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-03-30.
Xiang et al. (Tue,) studied this question.