Data from Enhanced <i>GAB2</i> Expression Is Associated with Improved Survival in High-Grade Serous Ovarian Cancer and Sensitivity to PI3K Inhibition

Abstract

<div>Abstract<p>Identification of genomic alterations defining ovarian carcinoma subtypes may aid the stratification of patients to receive targeted therapies. We characterized high-grade serous ovarian carcinoma (HGSC) for the association of amplified and overexpressed genes with clinical outcome using gene expression data from 499 HGSC patients in the Ovarian Tumor Tissue Analysis cohort for 11 copy number amplified genes: <i>ATP13A4</i>, <i>BMP8B</i>, <i>CACNA1C</i>, <i>CCNE1</i>, <i>DYRK1B</i>, <i>GAB2</i>, <i>PAK4</i>, <i>RAD21</i>, <i>TPX2</i>, <i>ZFP36</i>, and <i>URI</i>. The Australian Ovarian Cancer Study and The Cancer Genome Atlas datasets were also used to assess the correlation between gene expression, patient survival, and tumor classification. In a multivariate analysis, high <i>GAB2</i> expression was associated with improved overall and progression-free survival (<i>P</i> = 0.03 and 0.02), whereas high <i>BMP8B</i> and <i>ATP13A4</i> were associated with improved progression-free survival (<i>P</i> = 0.004 and <i>P</i> = 0.02). <i>GAB2</i> overexpression and copy number gain were enriched in the AOCS C4 subgroup. High <i>GAB2</i> expression correlated with enhanced sensitivity <i>in vitro</i> to the dual PI3K/mTOR inhibitor PF-04691502 and could be used as a genomic marker for identifying patients who will respond to treatments inhibiting PI3K signaling. <i>Mol Cancer Ther; 14(6); 1495–503. ©2015 AACR</i>.</p></div>