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

作者：Egler Rachel A; Li Yiting; Dang Tu Anh T; Peters Tricia L; Leung Eastwood; Huang Shixia; Russell Heidi V; Liu Hao; Man Tsz Kwong^*

来源：Proteomics - Clinical Applications, 2011, 5(9-10): 532-541.

DOI：10.1002/prca.201000089

• Biomarkers
• Cytokines and chemokines
• Neuroblastoma
• Relapse

Purpose: 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.
Experimental design: In this study, we developed an integrated proteomic approach to identify plasma biomarkers for HRNB.
Results: 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.
Conclusion and clinical relevance: 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.

• 出版日期2011-10