SENSITIVITY AND SPECIFICITY OF POTENTIAL BLOOD BIOMARKERS FOR ENDOMETRIOSIS

Endometriosis is a common, incurable gynecologic disease of unknown etiology, which causes incapacitating pain during menses and infertility. There are no specific non-invasive diagnostic tests for endometriosis, therefore diagnosis is currently done by laparoscopy. The main goal of the present study is to further evaluate previously identified blood biomarkers of endometriosis, and to investigate their potential as targets for a molecular-based diagnostic assay. Women with endometriosis and controls were recruited by collaboration with local hospitals. Disease status was determined by surgery following ASRM criteria. Peripheral blood samples were obtained from which total RNA and serum were isolated. Real-time quantitative RT-PCR was used to determine gene expression levels of candidate genes in peripheral blood lymphocytes of patients and controls. Evidence Investigator BioChip Arrays (Randox, Inc.) were used to measure levels of reproductive hormones (e.g., estradiol, progesterone, testosterone, and prolactin). Differences in gene expression between groups were determined using t-test. Sensitivity, specificity, positive likelihood ratios, odds ratios, and areas under receiver operating characteristic (ROC) curves were calculated for each gene at different cutoff values. Reproductive hormones and gene expression levels were correlated to test the direction and strength of relationships. Significant differences in mean normalized Ct values between patients and controls were observed for three out of nine genes tested. ROC analysis results supported the potential value of at least two genes for the diagnosis of endometriosis (i.e., LOXL1: sensitivity >60%; specificity >81%; area under ROC=0.82; OR=8.1; P4HA: sensitivity >64%; specificity >69%; area under ROC=0.63; OR=3.4). There were no correlations between gene expression of these potential biomarkers and serum levels of estrogen and progesterone in patients and controls. These data suggest the possibility of using molecular biomarkers in blood for the detection of endometriosis. Follow up studies are necessary to validate these biomarkers as specific non-invasive diagnostic targets for this disease. Supported by: NIH R01 5 HD050559-1; NIH/MBRS S06-GM08239; NIH/NCRR/RCMI 2-G12 RR03050 (platform)