SRS387 - MLN64/StarD3 and StarD3NL in pancreatic cancer

Abstract Background MLN64/StarD3 (Metastatic Lymph Node 64, also known as StAR-related lipid transfer domain-3) has been associated with tumour spread in certain cancer types including breast and gastric cancers. It is often co-amplified with ERBB2 in HER2-overexpressing breast cancer. MLN64 N-terminal sequence shares a similarity with StarD3NL, a protein without the START lipid-transfer domain. MLN64 and StarD3NL are thought to regulate intracellular cholesterol distribution by facilitating the formation of endoplasmic reticulum (ER)-endosome membrane contact sites (MCSs). The role of MLN64 and StarD3NL in human pancreatic cancer remains unexplored. This study investigated the expression profiles of MLN64, StarD3NL, and the ERBB family in pancreatic cancer patients and their associations with clinical outcomes. Materials and Methods A cohort of 223 pancreatic cancer patients was enrolled. The expression of MLN64, StarD3NL, in conjunction with ERBB family members were quantified, with matched follow-up data collected for survival analysis. Results MLN64 expression was significantly upregulated in pancreatic tumour tissues compared with adjacent normal tissues (P < 0.01). MLN64 significantly correlated with StarD3NL expression (R = 0.362, P < 0.0001). Both MLN64 and StarD3NL significantly correlated with HER4 expression (R = 0.438, P < 0.01 and R = 0.397, P < 0.0001) respectively. Patients with a respective high expression of MLN64 or StarD3NL had a marginally shorter survival. However, the integrated expression pattern of MLN64 and StarD3NL revealed a statistically significant association with reduced disease-free survival (DFS) (P < 0.01). Conclusions This study is the first to show that integrated expression of MLN64 and StarD3NL is associated with poor prognosis in patients with pancreatic cancer and may serve as a prognostic biomarker.