A structured proteomic approach identifies 14-3-3Sigma as a novel and reliable protein biomarker in panel based differential diagnostics of liver tumors

作者：Reis Henning; Puetter Carolin; Megger Dominik A; Bracht Thilo; Weber Frank; Hoffmann Andreas C; Bertram Stefanie; Wohlschlaeger Jeremias; Hagemann Sascha; Eisenacher Martin; Scherag Andre; Schlaak Joerg F; Canbay Ali; Meyer Helmut E; Sitek Barbara; Baba Hideo A^*

来源：Biochimica et Biophysica Acta-Proteins and Proteomics, 2015, 1854(6): 641-650.

DOI：10.1016/j.bbapap.2014.10.024

• Label free proteomics
• 14-3-3Sigma
• Stratifin
• Hepatocellular carcinoma
• Biomarker panel
• Immunohistochemistry

Hepatocellular carcinoma (HCC) is a major lethal cancer worldwide. Despite sophisticated diagnostic algorithms, the differential diagnosis of small liver nodules still is difficult While imaging techniques have advanced, adjuvant protein-biomarkers as glypican3 (GPO), glutamine-synthetase (GS) and heat-shock protein 70 (HSP70) have enhanced diagnostic accuracy. The aim was to further detect useful protein-biomarkers of HCC with a structured systematic approach using differential proteome techniques, bring the results to practical application and compare the diagnostic accuracy of the candidates with the established biomarkers.
After label-free and gel-based proteomics (n = 18 HCC/corresponding non-tumorous liver tissue (NTLT)) biomarker candidates were tested for diagnostic accuracy in immunohistochemical analyses (n = 14 HCC/NTLT). Suitable candidates were further tested for consistency in comparison to known protein-biomarkers in HCC (n = 78), hepatocellular adenoma (n = 25; HCA), focal nodular hyperplasia (n = 28; FNH) and cirrhosis (n = 28).
Of all protein-biomarkers, 14-3-3Sigma (14-3-3S) exhibited the most pronounced up-regulation (58.8x) in proteomics and superior diagnostic accuracy (73.0%) in the differentiation of HCC from non-tumorous hepatocytes also compared to established biomarkers as GPO (64.7%) and GS (45.4%). 14-3-3S was part of the best diagnostic three-biomarker panel (GPO, HSP70, 14-3-3S) for the differentiation of HCC and HCA which is of most important significance. Exclusion of GS and inclusion of 14-3-3S in the panel (>1 marker positive) resulted in a profound increase in specificity (+44.0%) and accuracy (+11.0%) while sensitivity remained stable (96.0%). 14-3-3S is an interesting protein biomarker with the potential to further improve the accuracy of differential diagnostic process of hepatocellular tumors. This article is part of a Special Issue entitled: Medical Proteomics.

• 出版日期2015-6
• 单位河北医科大学