Abstract LB-451: Detection of urinary HE4 as a biomarker for epithelial ovarian cancer

Abstract

Human epididymis protein 4 (HE4) has been shown to be a promising serum biomarker for epithelial ovarian cancer (EOC). Recently, Hellstrom et al. reported the detection of HE4 in urine as a biomarker for ovarian neoplasms (Cancer Lett.2010;296:43–8). We investigated the feasibility of urinary HE4 in detection of EOC in a pilot study. METHODS: This retrospective study measured the HE4 levels in urine samples obtained from an institutional review board-approved sample bank. HE4 was measured with HE4 EIA (Fujirebio Diagnostics, Inc.). Creatinine was measured via colorimetric determination by the Jaffe Reaction and used to normalize the HE4 levels. Clinical diagnosis of the subjects was based on the pathological diagnosis. Single-point urine samples were analyzed from 232 subjects; 72 with EOC or low malignant potential tumors and 160 with benign disease. RESULTS: The medians of HE4 levels in subjects with EOC and with benign disease were 29833 pmol/L (95% Confidence Interval (CI): 21185–54728) and 8515 pmol/L (95% CI: 7077–9314) respectively. The medians of HE4/Creatinine ratios in subjects with EOC and with benign disease were 420 (95% CI: 269–491) and 75 (95% CI: 68–83), respectively. Both the medians of HE4 levels and HE4/Creatinine ratios in EOC subjects were significantly higher than that in subjects with benign disease (P<0.0001 in Median test). Receiver operator characteristic (ROC) analysis showed that areas under the curve (AUC) were 0.87 for HE4/Creatinine ratio (95% CI = 0.81–0.92) and 0.83 for HE4 level (95% CI = 0.76–0.89). There was no significant difference between the AUC for HE4 level and HE4/Creatinine ratio (P>0.05). Using the shoulder point of each ROC curve as the cut-off, the cut-off values were 152.5 for HE4/Creatinine ratio and 19161 pmol/L for HE4 level respectively. The sensitivity, specificity, positive predictive value and negative predictive value at the set cut-off values were 70.8% (95% CI = 58.9% – 81.0%), 93.1% (95% CI = 88.0% – 96.5%), 82.3% and 87.6% for HE4/Creatinine ratio, and 65.3% (95% CI = 53.1% – 76.1%), 89.4% (95% CI = 83.5% – 93.7%), 73.4% and 85.1% for HE4 level, respectively. Concordance rates versus clinical diagnosis were 86.2% for HE4/creatinine ratio and 81.9% for HE4 level. CONCLUSIONS: This pilot study demonstrated the utility of urinary HE4 level alone or HE4/Creatinine ratio as potential biomarkers for the detection of EOC. The HE4/Creatinine ratio appeared to be better than the HE4 level in correlating with the clinical pathological diagnosis of EOC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-451. doi:10.1158/1538-7445.AM2011-LB-451

Identification and Characterization of Aptamers Targeting Ovarian Cancer Biomarker Human Epididymis Protein 4 for the Application in Urine

“…This is observed by using currently available immunoassays. These conventional tests sometimes require application of creatinine as an internal standard for volume normalization [20,38]. The aptamers combine many advantages, they are low-molecular-weight substances, with high affinity, specificity and production at low cost.…”

“…The results further proved the concept of utilization of aptamers as diagnostic probes in urine for the development of future OC urine tests. The mean urine levels of urine HE4 present in patients with ovarian cancer described in literature are 28.56 nM [21] and 29.83 nM [38]. The cut-off value which is able to distinguish healthy individuals from cancer patients is approximately 13 nM [23], so binding of aptamers in urine should ideally be observed at concentrations >13 nM urinary HE4, which correspond to cancer patients.…”