Proteome Multimarker Panel With Multiple Reaction Monitoring–Mass Spectrometry for Early Detection of Hepatocellular Carcinoma

Abstract

There is an urgent need for new biomarkers that address the shortcomings of current screening methods which fail to detect a large proportion of cases with hepatocellular carcinoma (HCC) at early stage. To develop a robust, multiple-biomarker panel based on multiple reaction monitoring–mass spectrometry with high performance in detecting early-stage HCC within at-risk populations. In the discovery set, 150 samples were analyzed to identify candidate biomarkers. The resulting list of candidates was tested in the training set (713 samples) to establish a multimarker panel, which was evaluated in the validation set (305 samples). We identified 385 serum HCC biomarker candidates in the discovery set and developed a multimarker panel consisting of 28 peptides that best differentiated HCC from controls. The area under the receiver operating characteristic curve of multimarker panel was significantly higher than alpha-fetoprotein (AFP) in the training (0.976 vs. 0.804; P ' 0.001) and validation (0.898 vs. 0.778; P ' 0.001) sets. In the validation set, this multimarker panel, compared with AFP, showed significantly greater sensitivity (81.1% vs. 26.8%; P ' 0.001) and lower specificity (84.8% vs. 98.8%; P ' 0.001) in detecting HCC cases. Combining AFP with the multimarker panel did not significantly improve the area under the receiver operating characteristic curve compared with the panel alone in the training (0.981 vs. 0.976; P = 0.37) and validation set (0.906 vs. 0.898; P = 0.75). Conclusion: The multiple reaction monitoring–mass spectrometry multimarker panel consisting of 28 peptides discriminates HCC cases from at-risk controls with high performance and may have potential for clinical application in HCC surveillance.