Multiple Biomarker Panels For Early Detection of Ovarian Cancer

Yurkovetsky, Zoya R.; Linkov, Faina; Malehorn, David E.; Lokshin, Anna

doi:10.2217/14796694.2.6.733

Cited by 39 publications

(34 citation statements)

References 64 publications

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“…Our previous studies (summarized in [13,53]), which investigated the roles of multi-marker panels in the development of ovarian cancer, another type of gynecologic cancer, came out with promising results. Future studies in this area should concentrate on examining the longitudinal changes in serum concentrations of these biomarkers and investigating their associations with treatment response, relapse, complications, and survival.…”

Section: Discussionmentioning

confidence: 99%

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

Yurkovetsky

Ta’asan

Skates

et al. 2007

Gynecologic Oncology

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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.

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Section: Discussionmentioning

confidence: 99%

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

Yurkovetsky

Ta’asan

Skates

et al. 2007

Gynecologic Oncology

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“…Therefore, a multimarker approach for detection and monitoring of disease status should have a great potential in the future (21). In this regard, several research groups have successfully linked fluorescent nanoparticles to peptides, proteins, and oligonucleotides (22).…”

Section: Discussionmentioning

confidence: 99%

Multiplex Targeting, Tracking, and Imaging of Apoptosis by Fluorescent Surface Enhanced Raman Spectroscopic Dots

Lee

Han

et al. 2007

Bioconjugate Chem.

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We have developed multifunctional fluorescent surface enhanced Raman spectroscopic tagging material (F-SERS dots) composed of silver nanoparticle-embedded silica spheres with fluorescent organic dye and specific Raman labels for multiplex targeting, tracking, and imaging of cellular/molecular events in the living organism. In this study, F-SERS dots fabricated with specific target antibodies (BAX and BAD) were employed for the detection of apoptosis. The F-SERS dots did not show any particular toxicity in several cell lines. The F-SERS dots could monitor the apoptosis effectively and simultaneously through fluorescent images as well as Raman signals in both cells and tissues with high selectivity. Our results clearly demonstrate that F-SERS dots can be easily applicable to multiplex analysis of diverse cellular/molecular events important for maintaining cellular homeostasis.

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“…10 A panel comprising 4 biomarkers has been recommended to achieve greater coverage of the heterogeneity of ovarian cancer. 11 Several biomarker panels have been proposed for improved sensitivity over CA125 alone. 11 We investigated 96 promising serum biomarkers using multiplex xMAP bead-based immunoassays (Luminex, Austin, Texas) to identify several promising 4-markers.…”

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confidence: 99%

Validation of a Biomarker Panel and Longitudinal Biomarker Performance for Early Detection of Ovarian Cancer

Simmons¹,

Clarke²,

Badgwell³

et al. 2016

Int J Gynecol Cancer

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Objectives Longitudinal multi-marker combinations have the potential to improve sensitivity while maintaining the high specificity required for early detection of ovarian cancer. The use of multiple markers to improve sensitivity over CA125 in longitudinal algorithms for early ovarian cancer detection requires the selection of markers with optimal discriminatory power and low longitudinal variance relative to disease-initiated changes. Our objective was to identify a multi-marker panel suitable for ovarian cancer, where each individual marker has its own baseline, permitting longitudinal algorithm development. Materials and methods In this retrospective study, we measured CA125, HE4, MMP-7, CA72-4, CA19-9, CA15-3, CEA and s-VCAM concentrations using immunoassays in pre-treatment sera from 142 stage I ovarian cancer cases and 5 annual samples each from 217 healthy controls. Following random division into training and validation sets, all possible biomarker combinations were exhaustively explored using linear classifiers, to identify the panel with greatest sensitivity for stage I disease at a high specificity of 98%. To evaluate longitudinal performance of the individual markers, the within-person over time and the between-person coefficient of variation (CV) were estimated. Hierarchical modeling across women of log-concentrations enabled borrowing of information across subjects to moderate variance estimates, given the small number of observations per subject. Results The four marker panel comprising CA125, HE4, MMP-7 and CA72-4 performed with the highest sensitivity (83.2%) at 98% specificity. The within-person CVs were lower for CA125, HE4, MMP-7 and CA72-4 (15%, 25%, 25% and 21% respectively) compared to their corresponding between-person CV (49%, 20%, 35% and 84% respectively) indicating baselines in healthy volunteers. Following simple log-transformations, within-volunteer variation across volunteers was modeled with a normal distribution, permitting parsimonious hierarchical modeling. Conclusions The multiplex panel chosen is suitable for early detection of ovarian cancer and the individual markers have their own baseline permitting longitudinal algorithm development.

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Multiple Biomarker Panels For Early Detection of Ovarian Cancer

Cited by 39 publications

References 64 publications

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

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

Multiplex Targeting, Tracking, and Imaging of Apoptosis by Fluorescent Surface Enhanced Raman Spectroscopic Dots

Validation of a Biomarker Panel and Longitudinal Biomarker Performance for Early Detection of Ovarian Cancer

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