Study of YAP as a prognostic marker for Triple-negative Breast Cancer in Indian Cohort

Abstract

Breast carcinoma is one of the most frequently occurring cancers in females, with high proportion of cancer associated deaths in countries like India. The invasive carcinoma is classified into four major molecular subtypes; Luminal A, Luminal B, HER2-positive, and TNBC. The prevalence of TNBC in Indian cohort is found to be up to 31%, which is significantly higher compared to Western populations. It is essential to investigate novel markers to profile this aggressive subset for a better prognosis. One such marker is the Yes-associated protein (YAP). YAP is a co-activator protein that is regulated by the Hippo signaling pathway. Prior studies have shown that YAP protein expression and its target signature expression in breast cancer patients significantly associates with recurrence in breast cancer patients as well as is responsible for epithelial-mesenchymal transition and stemness enrichment of breast epithelial cell lines. This implicates YAP plays a role in breast cancer progression and prognosis and is a potential biomarker. To understand TNBC specific association of YAP with progressive disease characteristics, 50 primary TNBC tissues were evaluated and analyzed for co-relation of YAP expression with clinical features and survival outcomes. YAP was localized in both tumor nuclei, and cytoplasm and its nuclear expression was associated with the presence of lymph node metastasis. Cytoplasmic YAP expression also inversely correlated tumor infiltrating lymphocytes levels. Kaplan-Meier curves revealed that high nuclear to cytoplasmic YAP levels associated with reduced overall survival. These results suggest that further research is needed to suggest that YAP could be a prognostic marker in TNBC patients.