Abstract

<div>Abstract<p><b>Purpose:</b> APOBEC3 DNA cytosine deaminase family members normally defend against viruses and transposons. However, deregulated APOBEC3 activity causes mutations in cancer. Because of broad expression profiles and varying mixtures of normal and cancer cells in tumors, including immune cell infiltration, it is difficult to determine where different APOBEC3s are expressed. Here, we ask whether correlations exist between <i>APOBEC3</i> expression and T-cell infiltration in high-grade serous ovarian cancer (HGSOC), and assess whether these correlations have prognostic value.</p><p><b>Experimental Design:</b> Transcripts for <i>APOBEC3G, APOBEC3B</i>, and the T-cell markers, <i>CD3D, CD4, CD8A, GZMB, PRF1</i>, and <i>RNF128</i> were quantified by RT-qPCR for a cohort of 354 HGSOC patients. Expression values were correlated with each other and clinical parameters. Two additional cohorts were used to extend HGSOC clinical results. Immunoimaging was used to colocalize APOBEC3G and the T-cell marker CD3. TCGA data extended expression analyses to additional cancer types.</p><p><b>Results:</b> A surprising positive correlation was found for expression of <i>APOBEC3G</i> and several T cell genes in HGSOC. Immunohistochemistry and immunofluorescent imaging showed protein colocalization in tumor-infiltrating T lymphocytes. High <i>APOBEC3G</i> expression correlated with improved outcomes in multiple HGSOC cohorts. TCGA data analyses revealed that expression of <i>APOBEC3D</i> and <i>APOBEC3H</i> also correlates with <i>CD3D</i> across multiple cancer types.</p><p><b>Conclusions:</b> Our results identify <i>APOBEC3G</i> as a new candidate biomarker for tumor-infiltrating T lymphocytes and favorable prognoses for HGSOC. Our data also highlight the complexity of the tumor environment with respect to differential <i>APOBEC</i> family gene expression in both tumor and surrounding normal cell types. <i>Clin Cancer Res; 22(18); 4746–55. ©2016 AACR</i>.</p></div>

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