Abstract P2-26-20: Marvel D3 and its associated junctional proteins in breast cancer

Abstract

Abstract Marvel D3 and its associated junctional proteins in breast cancer Wenxiao Ji, Wen G. Jiang, Tracey A. Martin CCMRC, Cardiff University School of Medicine, Cardiff, Wales, UK Introduction. Marvel (Membrane Associated Domain Containing) proteins are a small family of proteins that are concentrated at the tight junction (TJ) region of epithelial and endothelial cells. They are important players in the formation and regulation of TJs. The Marvel protein family has three members, Marvel-D1, Marvel-D2 and Marvel-D3, all known to be TJ components. Marvel-D3 is more prominent in TJ regulation, by interacting widely with other proteins that co-localised at TJs. In the present study, we have examined the expression of Marvel-D3 and its splicing variants, their relationship with other known interactive TJ partners in breast cancer and in disease progression and clinical outcome. Methods. Marvel-D3 and its variants were quantified in a breast cancer cohort that contained both normal and tumour tissues. The expression was analysed together with the known Marvel-D3 interactive molecules available in our database of the same cohort. The profile of the expression of the molecules was also integrated to search for a pattern of the expression that may have clinical significance including the survival of the patients. Results. Marvel-D3 had significantly high levels in breast cancer tissues than normal tissues (p=0.011). The difference between normal and tumour tissues for two Marvel-D3 variants were not statistically significant. Of all the known Marvel-D3 interactive proteins that were available for analyses, we identified thirteen with viability in integrated analyses; they include the JAM family members, Marvel-D2, occludin, the zonula occluden family members, small number of the claudin family members and cingulin, all being important TJ components. The integrated expression of these Marvel-D3 partners presented a highly significant predictive power for the overall survival of the patients (RUC=0.821, p< 0.0001). Stratifying the patients based on the profile has a significant value in evaluating survival (survival rate 95.7% with favourable expression versus 57.1% unfavourable, during the followup period). This predictive power is independent of other clinical and hormonal receptor status (p< 0.001, HR=1.226 (95% CI 1.094-1.373)). We have also noted that this predictive value is applicable to subtypes of the breast cancer and hormone receptor status with similar predictive power. Conclusion. Expression of Marvel-D3, a TJ component, together with its interactive TJ partners, including both transmembrane and intracellular subcoat proteins, form an important clinical indicator for clinical progression of breast cancer. Citation Format: WENXIAO JI, Wen G. Jiang, Tracey A. Martin. Marvel D3 and its associated junctional proteins in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-20.