Epithelial-mesenchymal transition polarization in ovarian carcinomas from patients with high social isolation

Abstract

Background: Social isolation has shown robust associations with clinical outcomes in the general population and in patients with cancer. In patients with ovarian cancer, social isolation has been found to be related to decreased survival and multiple biomarkers supporting tumor progression. However, to the authors' knowledge, little is known regarding the relationship between social isolation and the molecular characteristics of ovarian tumors. Herein, the authors have used genome-wide transcriptional profiling to quantify associations between social isolation and epithelial-mesenchymal transition (EMT) polarization in ovarian tumors and transcriptome-driven, promoter-based bioinformatics analyses to identify gene regulatory pathways that may potentially underlie these changes. Methods: Tumor was sampled during primary surgical resection and immediately frozen in liquid nitrogen. After RNA extraction, microarray analysis of the transcriptome was performed and samples were analyzed to assess associations between EMT-related gene transcripts and social isolation (as indicated by a Social Provisions Scale Attachment subscale score <15). Convergent validation was provided by a promoter-based bioinformatic analysis of transcription factor activity. Results: Primary analyses of 99 women demonstrated a lower average expression of gene transcripts previously associated with epithelial differentiation in women with high social isolation (−0.143 ± 0.048 log2 mRNA abundance; P =.004), but no difference in mesenchymal differentiation as a function of social isolation (+0.007 ± 0.0064 log2 mRNA abundance; P =.900). Upregulated activity was shown for 3 of the 4 targeted EMT-related transcription factors, including GATA4 (P =.014); SMAD2, SMAD3, and/or SMAD4 (P