Abstract 4389: Glycogen synthase kinase 3A (GSK3A) gene alterations are negatively correlated with overall and disease-free survival in breast cancer patients: In silico analysis

Abstract

Abstract Breast cancer is a heterogeneous disease and most widespread malignancy in women. It is one of three leading causes of deaths worldwide, together with lung and colon cancer. Glycogen synthase kinase 3 (GSK3) is a serine/threonine protein kinase involved in glucose regulation, inflammation, immune responses, proliferation, migration and apoptosis. GSK3 is expressed in all mammalian tissues and has a role in diseases including mood disorders, Alzheimer disease, diabetes and cancer. GSK3A and GSK3B are two isoforms, encoded by distinct genes and are 98% identical within their kinase domain. Gene knockout studies demonstrate that the two isoforms are not completely redundant, but perform similar functions in several settings. So far, very little is known about GSK3A role in cancer. We analyzed correlation of GSK3A gene mutations and copy number changes with overall and disease-free survival in breast cancer patients using cBioPortal for cancer genomics. Fourteen datasets for breast cancer studies were analyzed and GSK3A alterations were found in seven datasets. These alterations included mutations (missense and truncating), amplifications and deep deletions; with amplifications being the most abundant alteration. Out of the seven datasets, three datasets showed significant negative correlation of GSK3A alterations with overall and disease-free survival in breast cancer patients. Kaplan-Meier curve analysis demonstrated that amplification of GSK3A gene is significantly correlated with poor overall and disease-free survival of breast cancer patients, specifically in estrogen receptor positive (ER+) tumors. Further, missense and truncating mutations leads to poor disease-free survival in patients with ER+ tumors and truncating mutation showed poor overall survival in patients with Her2+ tumors. Collectively, analysis of GSK3A genomic profile in breast cancer patients provides a novel insight that GSK3A is crucial in the biological behavior and/or pathogenesis of breast cancer and hence is an important therapeutic target for breast cancer treatment. Citation Format: Jasmeet Kaur, Karandeep Kaur. Glycogen synthase kinase 3A (GSK3A) gene alterations are negatively correlated with overall and disease-free survival in breast cancer patients: In silico analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4389.