SRS123 - Clinical relevance of MarvelD2 as a prognostic biomarker in clinical breast cancer

Abstract Introduction MarvelD2 (Tricellulin), a MARVEL domain protein seen at tricellular regions, is essential for paracellular barrier integrity. Its dysregulation may disturb polarity and permeability and promote epithelial–mesenchymal transition (EMT), suggesting a role in cancer development and progression. Methods In a cohort of breast cancer tissues, we assessed MarvelD2 expression using quantitative transcript analysis and examined its association with prognosis in relation to tumour staging, molecular subtypes and hormonal receptor status. Results MarvelD2 expression was found to be highly aberrant in breast tumours when compared with normal mammary tissues (P = 0.0126). High MarvelD2 was associated with poorer overall survival (P = 0.014), particularly in ER-positive (P = 0.007 versus ER negative), HER2-negative (P = 0.023 versus HER2 positive), EGFR-negative (P = 0.020 versus EGFR positive) and HER4-negative (P = 0.015 versus HER4 positive) subgroups. Disease-free survival (DFS) also tended to be reduced in patients with high MarvelD2 (P = 0.067), with this trend being significant in EGFR-negative (P = 0.009), HER4-negative (P = 0.049) patients and in patients with low levels of PGR (P = 0.006). Across molecular subtypes, high MarvelD2 predicted poorer prognosis in non-triple-negative breast cancers (P = 0.017), especially in ER-positive/HER2−negative tumours (P = 0.024). Multivariate Cox regression identified MarvelD2 expression and aromatase levels as independent prognostic factors. High MarvelD2 conferred a significantly increased risk of death (HR = 13.07, 95% c.i.: 2.10–81.47, P = 0.006), while elevated aromatase was similarly linked to adverse outcomes (HR = 38.32, 95% c.i.: 2.34–627.65, P = 0.011). Conclusions MarvelD2 has significant clinical relevance in breast cancer. Its expression correlates with both overall and disease-free survival, supporting its potential as a prognostic biomarker and therapeutic target.