SRS126 - MLN64 and StarD3NL highly correlated with the autophagy marker SQSTM1 and BECN1 in breast cancer, and indicate prognostic and therapeutic potential

Abstract Introduction MLN64 (Metastatic Lymph Node 64) and its homologue STARD3NL (STARD3 N-Terminal Like) are regulators of intracellular cholesterol transport. Cholesterol depletion is known to induce autophagy, while its receptors, SQSTM1, mediate lipophagy, linking lipid metabolism with autophagy. In this study, we investigated the potential interplay between MLN64, STARD3NL, and autophagy markers, as well as their clinical implications in breast cancer. Methods A freshly frozen breast cancer cohort (n = 160) comprising tumour and background tissues was transcribed into cDNA. Transcript levels of MLN64, STARD3NL, SQSTM1, and BECN1 were quantified. Bioinformatic analyses were performed in relation to patient’s clinical outcome factors. Results MLN64 expression was significantly correlated with SQSTM1 (R = 0.376, P = 1.3 × 10⁻⁵) and BECN1 (R = 0.374, P = 1.5 × 10⁻⁵) in breast cancer tissues. Comparable correlations were also observed between STARD3NL and SQSTM1 (P = 1.7 × 10⁻⁵) as well as BECN1 (P = 6.4 × 10⁻⁵). These associations with autophagy markers were diminished or absent in normal breast tissues. Importantly, the integrated bioinformatics analysis identified MLN64, STARD3NL, and BECN1 as a combined prognostic marker (AUC = 0.716, P = 0.002), significantly predicting overall survival (P = 3.5 × 10⁻⁵) and disease-free survival (P = 4.0 × 10⁻⁵). The predictive power was strongly linked to oestrogen receptor status and was more pronounced in patients with low aromatase levels (P = 7.44 × 10⁻⁷). Conclusions MLN64 and STARD3NL are strongly associated with autophagy markers and collectively demonstrate significant clinical relevance and hold prognostic potential in breast cancer.