Abstract PS6-62: Clinical implications of epithelial protein lost in neoplasm (EPLIN) associated proteins in breast cancer
Authors: Sanders Andrew James , Gong Wenjing , Zeng Jianyuan , Sun Ping , Martin Tracey Amanda , Mansel Robert Edward , Davies Eleri , Jiang Wen Guo 
Published: February 2021

Background. EPLIN, Epithelial Protein Lost In Neoplasm, also known as LIMA1 (LIM Domain And Actin Binding 1) is a cytoskeletal protein involved in the regulation of cellular actin dynamics (1). The protein has been shown to be lost or reduced in a wide range of cancer cells and reduced expression has been noted in a number of human solid cancers, including breast cancer. The reduction of EPLIN has been shown to be linked to poor prognosis of patients with breast cancer (2). Although EPLIN is known to regulate the cytoskeleton and subsequently certain cellular functions, the intercellular coordination during regulation is not fully understood with a number of potential partners implicated, including the CTNN family, CDH family and paxillin. In the present study, we have evaluated the connections between EPLIN and a number of protein partners together with their larger families in the context of clinical breast cancer.

Methods. The gene transcripts of EPLIN and its potential partners were quantitatively determined in a Cardiff cohort of human breast cancer, which forms part of a database and is supported by clinical, pathological information. The molecules were cross correlated and explored for the individual and most importantly collective power in their link with patient’s clinical outcomes.

Results. EPLIN, previously shown to be expressed at a reduced level in tumour compared to normal mammary tissues, exhibited an intimate correlation with the larger CTNN family and the cadherin family, namely with cadherin-1 (p&lt;0.0001) and alpha- and beta-catenins (p&lt;0.0001); there was no correlation with gamma-catenin (p&gt;0.05). Of the protein phosphatase protein family, EPLIN was significantly correlated with two of the PTPs that have cell-cell adhesive functions, namely PTPRM and PTPRK. One of the most interesting findings was the relationship between EPLIN and tight junction (TJ) protein family members in that 27 of 35 TJ molecules, including the claudin/TAMP/JAM family members were found to be highly correlated with EPLIN. It is noteworthy that EPLIN was inversely correlated with SIPA1 (Signal-induced proliferation-associated protein 1) (r= -0.23, p=0.03), one of the few known intracellular TJ regulators. Despite the importance of caveolin in EPLIN’s function, no significant connection was found between the two. From the comprehensive network of EPLIN partner families, we have identified a total of 12 key partner proteins, of which the expression pattern of the protein network was significantly correlated with overall survival (141 (136-146) months for favourable expression pattern vs 111 (92-130) months with unfavourable pattern, p&lt;0.001, Log ranked). Similarly, the network expression pattern also appeared as a significant predictor of disease-free survival (p&lt;0.0001). Multivariate analyses have indicated that the EPLIN network protein pattern is an independent prognostic factor for overall survival and disease-free survival.

Discussion. EPLIN is a cytoskeletal associated protein that is reduced in solid tumours. EPLIN is well connected to the cell-cell adhesion protein complex and tight junction protein complex as well as their regulators, which can be seen from the clinical cohort. Key members of the EPLIN interaction network have a strong power to predict the clinical outcome of patients with breast cancer. Collectively, this study indicates that EPLIN partner proteins are important factors in the development of breast cancer as well as prognostic indicators.

Reference1. Maul RS and Chang DD. EPLIN, epithelial protein lost in neoplasm. Oncogene. 1999, 18:7838.

Reference2. Jiang WG, Martin TA, Lewis-Russell JM et al, Eplin-alpha expression in human breast cancer, the impact on cellular migration and clinical outcome. Mol Cancer, 2008, 7, 71

Citation Format: Andrew James Sanders, Wenjing Gong, Jianyuan Zeng, Ping Sun, Tracey Amanda Martin, Robert Edward Mansel, Eleri Davies, Wen Guo Jiang. Clinical implications of epithelial protein lost in neoplasm (EPLIN) associated proteins in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-62.