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- Title
Biobehavioral modulation of the exosome transcriptome in ovarian carcinoma.
- Authors
Lutgendorf, Susan K.; Thaker, Premal H.; Arevalo, Jesusa M.; Goodheart, Michael J.; Slavich, George M.; Sood, Anil K.; Cole, Steve W.
- Abstract
<bold>Background: </bold>Social factors in the patient macroenvironment have been shown to influence molecular events in the tumor microenvironment and thereby influence cancer progression. However, biomarkers providing a window into the longitudinal effects of biobehavioral factors on tumor biology over time are lacking. Exosome analysis is a novel strategy for in vivo monitoring of dynamic changes in tumor cells. This study examined exosomal profiles from patients with low or high levels of social support for epithelial-mesenchymal transition (EMT) polarization and gene expression related to inflammation and β-adrenergic signaling.<bold>Methods: </bold>Exosomes were isolated from plasma sampled from a series of 40 women before primary surgical resection of advanced-stage, high-grade ovarian carcinoma. Samples were selected for analysis on the basis of extremes of low and high levels of social support. After exosomal isolation and RNA extraction, a microarray analysis of the transcriptome was performed.<bold>Results: </bold>Primary analyses identified significant upregulation of 67 mesenchymal-characteristic gene transcripts and downregulation of 63 epithelial-characteristic transcripts in patients with low social support; this demonstrated increased EMT polarization (P = .0002). Secondary analyses using promoter sequence bioinformatics supported a priori hypotheses linking low social support to 1) increased activity of cyclic adenosine monophosphate response element binding protein (CREB)/activating transcription factor (ATF) family transcription factors that mediate the β-adrenergic response to catecholamines via the cyclic adenosine monophosphate/protein kinase A signaling pathway (mean fold change for CREB: 2.24 ± 0.65; P = .0019; mean fold change for ATF: 2.00 ± 0.55; P = .0049) and 2) increased activity of the proinflammatory nuclear factor κB/Rel family of transcription factors (mean fold change: 2.10 ± 0.70; P = .0109).<bold>Conclusions: </bold>These findings suggest the possibility of leveraging exosomes as a noninvasive assessment of biobehavioral factors to help to direct personalized treatment approaches. Cancer 2018;124:580-6. © 2017 American Cancer Society.
- Subjects
OVARIAN cancer diagnosis; OVARIAN cancer treatment; SOCIAL support; ADRENERGIC receptors; QUALITY of life; OVARIAN tumors; PROTEINS; RESEARCH funding; DNA-binding proteins; GENE expression profiling; EXOSOMES
- Publication
Cancer (0008543X), 2018, Vol 124, Issue 3, p580
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.31078