Thymosin β4, a Potential Marker of Malignancy and Prognosis in Hepatocellular Carcinoma

Background: The lack of effective early diagnostic markers is an obstacle in clinical diagnosis and treatment of hepatocellular carcinoma (HCC). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an increasing popular approach for identification of clinically relevant parameters including biomarkers.

Patients And Methods: 540 subjects, including 274 HCC, 119 liver cirrhosis, 89 hepatitis, and 58 healthy volunteers were enrolled. MALDI-TOF MS was used to select potential novel biomarkers from serum of HCC patients. Its clinical application was evaluated by experiments and clinical data analysis.

Results: We identified Thymosin β4 (Tβ4) in serum by MALDI-TOF MS. The expression of Tβ4 was detected up-regulating in HCC cells and tissues which enhanced motility of HCC cells. More important, the level of serum Tβ4 was significantly elevated in HCC patients. The AUROC showed the optimum diagnostic cut-off was 1063.6 ng/mL, ROC and 95% CI of Tβ4 (0.908; 0.880-0.935) were larger than that of serum AFP (0.712; 0.662-0.762;  < 0.001). The sensitivity (91.3% vs 83.1%) and specificity (81.2% vs 20.3%) of serum Tβ4 were higher than alpha-fetoprotein (AFP). In AFP-negative HCC, the sensitivity could reach to 80.5%. ROC analysis showed serum Tβ4 had a better performance compared with AFP in distinguishing early-stage and small HCC. Tβ4 is correlated with TNM stage ( = 0.016) and vascular invasion ( = 0.005). Survival analysis indicated the survival time of Tβ4 positive patients was shorter (  0.001). Cox analysis suggested Tβ4 could be an independent factor for HCC prognosis.

Conclusion: Tβ4 may serve as a novel biomarker for HCC diagnosis and prognosis.