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An integrated proteomic approach to identifying circulating biomarkers in high-risk neuroblastoma and their potential in relapse monitoring.

ABSTRACT: Despite intensive treatment regimens, overall survival for high-risk neuroblastoma (HRNB) is still poor. This is in part due to an inability to cure the disease once a patient has reached clinical relapse. Identifying plasma biomarkers of active disease may provide a way of relapse monitoring in HRNB.In this study, we developed an integrated proteomic approach to identify plasma biomarkers for HRNB.We identified seven candidate biomarkers (SAA, APOA1, IL-6, EGF, MDC, sCD40L and Eotaxin) for HRNB. These biomarkers were then used to create a multivariate classifier of HRNB, which showed a specificity of 90% (95% confidence interval (CI), 73%, 98%), and a sensitivity of 81% (95%CI, 54%, 96%) for classifying HRNB in a training set. When evaluated on independent test samples, the classifier exhibited 86% accuracy (95% CI, 42%, 100%) of identifying diagnostic samples, and 86% accuracy (95% CI, 70%, 100%) of detecting post-diagnosis longitudinal samples that having active disease.Further validation of these biomarkers may improve patients' outcomes by developing a simple blood test for the detection of relapse prior to the development of clinically evident disease. Understanding the role of these biomarkers in immune surveillance of neuroblastoma may also provide a new direction of therapeutic strategies.

SUBMITTER: Egler RA

PROVIDER: S-EPMC3685293 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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An integrated proteomic approach to identifying circulating biomarkers in high-risk neuroblastoma and their potential in relapse monitoring.

Egler Rachel A RA Li Yiting Y Dang Tu Anh T TA Peters Tricia L TL Leung Eastwood E Huang Shixia S Russell Heidi V HV Liu Hao H Man Tsz-Kwong TK

Proteomics. Clinical applications 20110907 9-10

<h4>Purpose</h4>Despite intensive treatment regimens, overall survival for high-risk neuroblastoma (HRNB) is still poor. This is in part due to an inability to cure the disease once a patient has reached clinical relapse. Identifying plasma biomarkers of active disease may provide a way of relapse monitoring in HRNB.<h4>Experimental design</h4>In this study, we developed an integrated proteomic approach to identify plasma biomarkers for HRNB.<h4>Results</h4>We identified seven candidate biomarke ...[more]

PMID: 21833997

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Project description:BackgroundProteomics-based technologies are emerging tools used for cancer biomarker discovery. Limited prospective studies have been conducted to evaluate the role of circulating proteins in colorectal cancer (CRC) development.MethodsA two-stage case-control proteomics study nested in the Shanghai Women's Health Study was conducted. A total of 1104 circulating proteins were measured in the discovery phase, consisting of 100 incident CRC cases and 100 individually matched controls. An additional 60 case-control pairs were selected for validation. Protein profiling at both stages was completed using the Olink platforms. Conditional logistic regression was used to evaluate the associations between circulating proteins and CRC risk. The elastic net method was employed to develop a protein score for CRC risk.ResultsIn the discovery set, 27 proteins showed a nominally significant association with CRC risk, among which 22 were positively and 5 were inversely associated. Six of the 27 protein markers were significantly associated with CRC risk in the validation set. In the analysis of pooled discovery and validation sets, odds ratios (ORs) per standard deviation (SD) increase in levels of these proteins were 1.54 (95% confidence interval (CI): 1.15-2.06) for CD79B; 1.71 (95% CI: 1.24-2.34) for DDR1; 2.04 (95% CI: 1.39-3.01) for EFNA4; 1.54 (95% CI: 1.16-2.02) for FLRT2; 2.09 (95% CI: 1.47-2.98) for LTA4H and 1.88 (95% CI: 1.35-2.62) for NCR1. Sensitivity analyses showed consistent associations for all proteins with the exclusion of cases diagnosed within the first two years after the cohort enrollment, except for CD79B. Furthermore, a five-protein score was developed based on the six proteins identified and showed significant associations with CRC risk in both discovery and validation sets (Discovery: OR1-SD = 2.46, 95% CI: 1.53-3.95; validation: OR1-SD = 4.16, 95% CI: 1.92-8.99).ConclusionsA panel of five protein markers was identified as potential biomarkers for CRC risk. Our findings provide novel insights into the etiology of CRC and may facilitate the risk assessment of the malignancy.

Dataset Information

An integrated proteomic approach to identifying circulating biomarkers in high-risk neuroblastoma and their potential in relapse monitoring.

Publications

An integrated proteomic approach to identifying circulating biomarkers in high-risk neuroblastoma and their potential in relapse monitoring.

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