Investigation of human cationic antimicrobial protein-18 (hCAP-18), lactoferrin and CD163 as potential biomarkers for ovarian cancer

Abstract

Background: Epithelial ovarian cancer is one of the leading causes ofgynaecological cancer morbidity and mortality in women. Early stageovarian cancer is usually asymptomatic, therefore, is often firstdiagnosed when it is widely disseminated. Currently availablediagnostics lack the requisite sensitivity and specificity to beimplemented as community-based screening tests. The identification ofadditional biomarkers may improve the diagnostic efficiency ofmultivariate index assays. The aims of this study were to characteriseand compare the ovarian tissue immunohistochemical localisation andplasma concentrations of three putative ovarian cancer biomarkers: humancationic antimicrobial protein-18 (hCAP-18); lactoferrin; and CD163 innormal healthy women and women with ovarian cancer.Methods: In this case-control cohort study, ovarian tissue and bloodsamples were obtained from 164 women (73 controls, including 28 womenwith benign pelvic masses; 91 cancer, including 21 women with borderlinetumours). Localisation of each antigen within the ovary was assessed byimmunohistochemistry and serum concentrations determined by ELISAassays.Results: Immunoreactive (ir) hCAP-18 and lactoferrin were identified inepithelial cells, while CD163 was predominately localised in stromalcells. Tissue ir CD163 increased significantly (P<0.05) with diseasegrade. Median plasma concentrations of soluble (s)CD163 weresignificantly greater in the cases (3220 ng/ml) than in controls (2488ng/ml) (P<0.01). Median plasma concentrations of hCAP-18 and lactoferrinwere not significantly different between cases and controls. Theclassification efficiency of each biomarker (as determined by the areaunder the receiver operator characteristic curve; AUC) was: 0.67 +/-0.04; 0.62 +/- 0.08 and 0.51 +/- 0.07 for sCD163, hCAP-18 andlactoferrin, respectively. When the 3 biomarkers were modelled usingstochastic gradient boosted logistic regression, the AUC increased to0.95 +/- 0.03.Conclusions: The data obtained in this study establishes thelocalisation and concentrations of CD163, hCAP-18, and lactoferrin inovarian tumours and peripheral blood. Individually, the 3 biomarkersdisplay only modest diagnostic efficiency as assessed by AUC. Whencombined in a multivariate index assay, however, diagnostic efficiencyincreases significantly. As such, the utility of the biomarker panel, asan aid in the diagnosis of cancer in symptomatic women, is worthy offurther investigation in a larger phase 2 biomarker trial.