Abstract
Abstract The continuous interplay between cancer cells and immune system allows an opportunity to identify cancer-specific biomarkers in immune cells. Here, we compare the transcriptomes of peripheral blood mononuclear cells (PBMCs) obtained from advanced stage ovarian cancer patients and healthy donors in a proof-of-concept study to identify ovarian cancer-specific biomarkers. PBMCs were collected from patients undergoing surgery with the gynecologic oncology service. RNA was extracted from the PBMCs of five patients (training set) with confirmed diagnosis of epithelial ovarian cancer and 4 health donor blood samples. Microarray analysis using Illumina platform was conducted and analyzed using the R statistical package. After data normalization, differentially expressed genes in the two cohorts were identified controlling for false discovery rate at 5 and 10%. The top ten up- and downregulated genes were selected. Gene ontology and pathway analysis led to identification of a Candidate Biomarker Panel (CBP) comprising of five of the ten genes that were most likely to serve as biomarkers for ovarian cancer. Validation of the CBP was achieved using PBMCs isolated from a separate group of six patients and healthy donors (test set) was performed using qPCR and flow cytometry and in vitro culture experiments. Bioinformatics analysis identified 391 genes that were up-regulated and 599 that were down-regulated. A set of five genes with high biomarker potential and were included in the CBP. All of the CBP genes were differentially expressed by 3-5 fold (p<0.03) in the cancer patient PBMCs as compared to healthy donors. Validation results for the CBP were similar between the training set and the test set. Co-culture experiments indicated differential expression of the CBP genes in healthy donor-derived PBMCs co-cultured with cancer cells. Continuous cross-talk between immune cells and abnormal tissues leads to changes in the immune cell transcriptome and proteome in response to a pathologic state. We demonstrate that the transcriptome and proteome of circulating immune cells is a repository for ovarian cancer-specific biomarkers. Our on-going studies are focused on validating the CBP in a larger cohort of samples obtained from healthy donors, ovarian cancer patients and subjects treated for benign gynecologic anomalies. Citation Format: Shitanshu Uppal, Arvinder Kapur, Mildred Felder, Erin Medlin, Hadi Shojaei, Jesus Gonzalez-Bosquet, Manish S. Patankar. Mining the circulating immune cell transcriptome for ovarian cancer-specific biomarkers: A proof of concept study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 893. doi:10.1158/1538-7445.AM2014-893
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