Thymosin β4, a potential marker of malignancy and prognosis in hepatocellular carcinoma

Abstract

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; p < 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 (p = 0.016) and vascular invasion (p = 0.005). Survival analysis indicated the survival time of Tβ4 positive patients was shorter (p < 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.

Keywords:

• Thymosin β4
• biomarker
• diagnosis
• prognosis
• hepatocellular carcinoma

Acknowledgements

The authors appreciated the support by medical innovation research special project of Shanghai [22Y11908600], National Nature Science Foundation of China [Grant Nos. 82173212 and 81301830], the development fund for Shanghai talents [2020065] and Shanghai key clinical specialty project [shslczdzk02402].

Ethical approval and consent to participate

The collection and use of clinical resources including HCC tissue, serum samples and follow-up data, which performed in accordance with guidelines was complied with the permission of Biomedical Ethics Committee of Navy Military Medical University (Shanghai, China). The written consent from each patient has been provided, which was conducted in accordance with the declaration of Helsinki.

Author contributions

WCW, XFZ, EJT and AJL: contribution to the conception and design of this study and manuscript drafting. LC, JQW and JYM: acquisition, analysis, and interpretation of the data. XFZ and BS: critical revision of the manuscript and final approval of the version to be published. All authors have read and approved the final manuscript.

Disclosure statement

The authors declare that they have no competing interests in this study.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.