Abstract Introduction StarD3NL (StAR Related Lipid Transfer Domain Containing-3 N-Terminal Like), also known as MENTHO, is a tethering protein. It allows the endoplasmic reticulum (ER) and late endosomes to make contact and to intracellularly transport cholesterol from ER to other endosomes and cytoplasmic membrane where cholesterol known to play a role in organising membrane integral proteins for their function. This is a role similarly held by MLN64 (Metastatic Lymph Node Gene 64 Protein) (also known as StarD3, StAR Related Lipid Transfer Domain Containing 3). We have previously established that MLN64 has an important role in the cell adhesion of cancer cells and a clinical role in clinical breast cancer. There is little knowledge on the expression of StarD3NL in breast cancer. Methods Quantitative PCR (qPCR) was used to assess transcript levels in a Cardiff cohort of breast cancer and normal tissues (151 samples) with a 10 year follow up. Clinical and pathological outcomes were compared and results analysed using Mann Whitney U test for comparisons, logistic regression and Kaplan-Meier’s methods for survival analyses Results StarD3NL levels were seen to be lower in patients with moderate and poor prognosis compared to those with good prognosis and lower in node positive tumours (p=0.046). When assessed against clinical outcome, it was found that patients who developed breast cancer related incidence had significantly lower levels of StarD3NL when compared with those who remained disease free (p=0.0086). This was reflected in the survival analysis in which patients with lower levels of StarD3NL had a significantly shorter disease free survival (DFS) (p=0.025, Hazard Ratio (HR)=0.329 (95% confidence internal 0.116-0.933)). A similar trend was seen with overall survival (OS) although this did not reach statistical significance. The link between StarD3NL and DFS was more prominent in HER2 positive and HER3 negative tumours, and in non-TNBC breast cancers. StarD3NL expression appears to be significantly correlated with MLN64 in both breast cancer (r=0.410, p0.001) and in normal mammary tissues (r=0.679, p0.001). This was observed in that the subgroup with low levels of MLN64 also demonstrated that StarD3NL had a more striking connection with DFS (p=0.009) and indeed overall survival (p=0.043). Conclusion StarD3NL appears to be significantly related to breast cancer patient disease free survival, which was pronounced in HER2 positive and HER3 negative tumour types; moreover, this change was linked to MLN64 expression. These data suggest that these two proteins could be an interesting target for future prognostic development. Citation Format: H. Y. Xiang, H. Y. Xiang, Y. R. Chen, C. Wang, X. Y. Li, F. Askr, T. A. Martin, K. Mokbel, W. G. Jiang. Steroidogenic acute regulatory protein related lipid transfer domain containing-3 n-terminal like(STARD3NL) expression in clinical breast cancer and its connection with metastatic lymph node 64 (MLN64) in 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 PS3-11-01.
Xiang et al. (Tue,) studied this question.
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