Development of multimarker panel for early detection of endometrial cancer. High diagnostic power of prolactin

Abstract

Objective-Endometrial carcinoma is the most common gynecologic cancer. Although the prognosis for endometrial cancer is generally good, cancers identified at late stages are associated with high levels of morbidity and mortality. Therefore, prevention and early detection may further reduce the burden of this challenging disease.Methods-A panel of 64 serum biomarkers was analyzed in sera of patients with stages I-III endometrial cancer and age-matched healthy women, utilizing a multiplex xMAP ™ bead-based immunoassay. For multivariate analysis, four different statistical classification methods were used: logistic regression (LR), separating hyperplane (SHP), k nearest neighbors (KNN), and Classification Tree (CART). For each of these classifiers a diagnostic model was created, based on the crossvalidation set consisting of sera from 115 patients with endometrial cancer and 135 healthy women.Results-Our data have demonstrated that patients with endometrial cancer have significantly different expression patterns of several serum biomarkers as compared to healthy controls. Prolactin was the strongest discriminative biomarker for endometrial cancer providing 98.3% sensitivity and 98.0% specificity alone. Our results have revealed that serum concentration of cancer antigens, including CA 125, CA 15-3, and CEA are higher in patients with Stage III endometrial cancer as compared to those with Stage I. In addition, we have shown that the expression of CA 125, AFP and ACTH is elevated in women with tumor grade 3 vs. grade 1. Furthermore, 5-biomarker panel Requests for reprints: Anna Lokshin, University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Ave., Pittsburgh, PA 15213. Phone: 412-623-7706; Fax: 412-623-1415; E-mail: lokshina@pitt.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (prolactin, GH, Eotaxin, E-selectin, and TSH) identified in this study, was able to discriminate endometrial cancer from ovarian and breast cancers with high sensitivity and specificity. NIH Public AccessConclusions-The ability of prolactin to accurately discriminate between cancer and control groups indicates that this biomarker could potentially be used for development of blood-based test for the early detection of endometrial cancer in high-risk populations. Combining the information on multiple serum markers using flexible statistical methods allows for achieving high cancer selectivity.

Molecular markers of endometrial carcinoma detected in uterine aspirates

“…Yurkovetsky et al identified that prolactin is a serum biomarker with sensitivity and specificity for EC. 15 They found that serum CA 125, CA 15-3 and CEA are higher in patients with Stage III disease when compared to Stage I, and a five-biomarker panel of prolactin, GH, eotaxin, E-selectin and TSH discriminated EC from ovarian and breast cancer. Nevertheless, none of these potential biomarkers has been validated nor reached the clinical practice.…”

Evaluation of a Multianalyte Profiling Assay and an Enzyme-Linked Immunosorbent Assay for Serological Examination of Epstein-Barr Virus-Specific Antibody Responses in Diagnosis of Nasopharyngeal Carcinoma

“…Therefore, if the proper components of EBV antigens, such as EA-D and EBNA1, were selected, both xMAP and ELISA assays could have relatively high sensitivity, specificity, and AUC for EBV serodiagnosis of NPC. The flexibility of the xMAP technology as well as its throughput ability gives it broad applications, such as cytokine and chemokine analysis, antibody screening, HLA typing, pathogen detection, and single-nucleotide polymorphism or mutation analysis (1,4,8,9,19,25,36). Our results showed that the xMAP assay is suitable for EBV antibody detection when proper biomarkers are used and provides valid serological profiles of EBV in NPC patients.…”

Increased expression of the prolactin receptor is associated with malignant laryngeal tumors

“…For example, studies on prostate cancer and head and neck cancer concluded that there was no correlation between PRL levels and cancer risk (18,19). However, Yurkovetsky et al showed that PRL was the strongest discriminative biomarker for endometrial cancer (20).…”