Abstract Introduction MarvelD1 (MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain containing-1) is a protein with multiple transmembrane helix and potential microtubule binding properties. It has been indicated to have a role in cell division and locates in the tight junctional regions of cells. Some evidence suggests that MarvelD1 plays a role in the development and progression of solid cancer but this is conflicting, namely that it exhibits a potential oncogenic role in pancreatic cancer and a tumour suppressor in hepatocellular carcinoma. There has been no report on the role of MarvelD1 in human breast cancer. Methods The expression of the MarvelD1 gene transcript and MarvelD1 protein in breast cancer were investigated by quantitative gene transcript analysis and immunohistochemistry respectively. MarvelD1 expression was analysed against clinical outcome, pathological factors, hormone receptor status and molecular subtypes of the patients. We created breast cancer cell models by knockdown the MarvelD1 with anti-MarvelD1 shRNA delivered by lentiviral approach. The biological responses following MarvelD1 knockdown were assessed including the rate of cell growth, cellular migration, cell adhesiveness and potential paracellular barrier functions of the breast cancer cells. Results Breast tumour tissues had a significantly higher level of MarvelD1 than normal mammary tissues (p=0.023). ERBB2/HER2 positive tumours had higher levels of MarvelD1 than HER2 negative tumours (p=0.0129). There was no significant difference between hormonal receptor subtypes (oestrogen receptor (ER) and progesterone receptor (PGR) positive and negative tumours). Amongst the main molecular subtypes, triple negative breast cancer demonstrated the lowest levels of MarvelD1. Patients with high levels of MarvelD1 had a significantly shorter overall survival (OS) compared with patients with low MarvelD1 (p=0.019, hazard ratio (HR) 0.304 (95% confidence interval 1.113-8.18). It is noteworthy that the OS and MarvelD1 link is more prominent in PGR negative (p=0.006), ERBB3/HER3 positive (p=0.007) and ERBB4/HER4 positive (p=0.026) tumours. We successfully created MarvelD1 knockdown breast cancer cell models by way of lentiviral based shRNA. There had been significant biological responses in cells with MarvelD1 knockdown including a markedly reduced cell growth rate, weakened matrix adhesion and cellular migration. Discussion MarvelD1, a membrane and microtubule associated protein, has a significant clinical relevance in breast cancer in which the expression levels have a link with the survival of the patients, and the link is to a degree dependent upon the receptor status. Experimental evidence further supports the connection between MarvelD1 and the aggressiveness of breast cancer cells. Citation Format: H. Y. Xiang, H. Y. Xiang, T. A. Martin, K. Mokbel, Y. H. Liu, W. G. Jiang. Marveld1 expression in breast cancer and the impact on the aggressive nature of breast cancer cells 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 PS2-12-28.
Xiang et al. (Tue,) studied this question.