Abstract P1-01-04: EPLIN and EPLIN responsive protein APOC3 in breast cancer

Abstract Introduction. EPLIN (Epithelial Protein Lost in Neoplasm, also known as LIMA1) is a cytoskeletal associated element and has been shown to act as a tumour suppressive molecule in breast cancer and a few other cancer types. Little is known about the regulatory and the responsive proteins for EPLIN. The present study has explored the potential EPLIN responsive proteins in cancer cells and the possible clinical connections in prognosis and treatment in breast cancer. Methods. EPLIN knockdown cell models were created by using lentiviral shRNA for EPLIN. The responsive proteins including phospho-proteins following EPLIN knockdown were systemically evaluated by MS based bioinformatics analysis. Clinical cohorts and tissue microarrays were used to evaluate the potential EPLIN interactive candidates at gene transcript and protein levels, respectively. The prognostic connection and therapeutic values were also explored. Results. Knockdown EPLIN resulted in active responses of a number of proteins, of which APOC3 (apolipoprotein C3) was amongst the top ones (both total level and phosphorylated proteins). In clinical cohort, APOC3 were found to be significantly correlated with EPLIN in breast tumour tissues (r=-0.218, p=0.042) but not in normal mammary tissues (p=0.555). APOC3 expression in breast tumour tissues was found to be higher in ER negative tumour (p=0.0058) and in PGR positive tumours (p=0.039), and also in those who died of breast cancer (p=0.016, versus those who remained disease free). The expression profile of the EPLIN related molecule identified patients with high survival risk in those who had PGR negative breast tumours (p=0.014, HR=1.374 (95%CI 1.007-1.875) and in triple negative breast tumours (TNBC) (p=0.045). Multivariate analysis revealed that the expression profile is an independent prognostic factor for PR negative patients (p=0.037) against other clinical factors. Finally, we explored the value of APOC3 and EPLIN in relation to patient’s response to drug treatments in a public database. It was clear that high levels of APOC3 in breast cancers rendered the patients with a significant chance of developing resistance to chemotherapies (p=0.000024) and this connection is independent on status of ER, ERBB2 and the molecular subtypes. Intriguingly, APOC3 was found to be a good indicator for sensitivity to anti-Her2 treatment (AUC=0.79, p=0.00076). Conclusion. The present study identifies a key EPLIN response protein, APOC3 which together with EPLIN forms an important prognostic factor for patients with breast cancer particularly in those with PR negative tumours. It also forms a theranostic indicator for patient’s response to drug treatment. Citation Format: Cai Wang,Tracey A. Martin, Jimmy J. Zeng, Amber X. Li, Eleri Davies, Fiona Ruge, Wen G. Jiang. EPLIN and EPLIN responsive protein APOC3 in breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-01-04.