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Randomized Controlled Trial
. 2012;7(3):e31989.
doi: 10.1371/journal.pone.0031989. Epub 2012 Mar 9.

Molecular prognostic prediction for locally advanced nasopharyngeal carcinoma by support vector machine integrated approach

Affiliations
Randomized Controlled Trial

Molecular prognostic prediction for locally advanced nasopharyngeal carcinoma by support vector machine integrated approach

Xiang-Bo Wan et al. PLoS One. 2012.

Abstract

Background: Accurate prognostication of locally advanced nasopharyngeal carcinoma (NPC) will benefit patients for tailored therapy. Here, we addressed this issue by developing a mathematical algorithm based on support vector machine (SVM) through integrating the expression levels of multi-biomarkers.

Methodology/principal findings: Ninety-seven locally advanced NPC patients in a randomized controlled trial (RCT), consisting of 48 cases serving as training set and 49 cases as testing set of SVM models, with 5-year follow-up were studied. We designed SVM models by selecting the variables from 38 tissue molecular biomarkers, which represent 6 tumorigenesis signaling pathways, and 3 EBV-related serological biomarkers. We designed 3 SVM models to refine prognosis of NPC with 5-year follow-up. The SVM1 displayed highly predictive sensitivity (sensitivity, specificity were 88.0% and 81.9%, respectively) by integrating the expression of 7 molecular biomarkers. The SVM2 model showed highly predictive specificity (sensitivity, specificity were 84.0% and 94.5%, respectively) by grouping the expression level of 12 molecular biomarkers and 3 EBV-related serological biomarkers. The SVM3 model, constructed by combination SVM1 with SVM2, displayed a high predictive capacity (sensitivity, specificity were 88.0% and 90.3%, respectively). We found that 3 SVM models had strong power in classification of prognosis. Moreover, Cox multivariate regression analysis confirmed these 3 SVM models were all the significant independent prognostic model for overall survival in testing set and overall patients.

Conclusions/significance: Our SVM prognostic models designed in the RCT displayed strong power in refining patient prognosis for locally advanced NPC, potentially directing future target therapy against the related signaling pathways.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Immunohistochemical staining of tissue biomarkers in locally advanced NPC.
The panel displayed the representative expression of 37 molecular biomarkers in tumor zone for locally advanced NPC (original magnification, ×400).
Figure 2
Figure 2. ROC curves plotted for patient outcome, using 38 tissue molecule expression scores, 3 serological biomarkers levels and SVM models, in training set (A), testing set (B) and overall patients (C).
In training set (A), at each immunohistochemical staining score of 38 tissue molecules and 3 serological biomarkers, the sensitivity and specificity for the outcome being studied were plotted, thus generating a ROC curve. The score, that closest to the point with both maximum sensitivity and specificity (0.0, 1.0), was selected as the cutoff point for further analysis.
Figure 3
Figure 3. Kaplan-Meier estimated of overall survival (OS) for SVM1, SVM2 and SVM3 models identified high and low risk to death subgroups in both testing set and overall patients.
For SVM1 model (A), a significant survival disadvange was observed for the high risk to death subgroup, which was identified by SVM1 model, in testing set (left panel) and overall patients (right panel). For SVM2 (B) and SVM3 model (C), a statistically OS difference was shown between high and low risk to death subgroups, which was indentified respectively by SVM2 and SVM3 model, in testing set (left panel) and overall patients (right panel).

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