Expression and prognostic impact of NTF3 and TrkC in hepatocellular carcinoma

Abstract

Background

Treatment of patients with NTRK fusion-positive cancers using first-generation tropomyosin-related kinase (Trk) inhibitors is associated with high response rates, regardless of tumor histology. However, there have been few studies on neurotrophin-3 (NTF3) and TrkC ligands in hepatocellular carcinoma (HCC).

Methods

We used immunohistochemistry to evaluate NTF3 and TrkC expression levels in tissue samples. Gene expression profiling interactive analysis was used to determine TrkC and NTF3 expression in HCC. Western blotting, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assays were utilized to analyze TrkC and NTF3 levels in HCC cell lines. Proliferation tests and cell migration were also explored.

Results

NTF3 and TrkC levels were lower in HCC tissue (median H- scores 149.09 and 54.60, respectively) than those in para-cancerous tissue (192.69 and 71.70, respectively); no statistical difference was found in the survival rate. Positive correlations were observed between NTF3 and TrkC levels in both HCC and para-cancerous tissues. Alpha-fetoprotein was the only clinical characteristic associated with TrkC levels. The transcription of NTF3 was lower in HCC samples compared to normal samples. NTF3 overexpression inhibited the proliferation of MHCC97-L and HepG2 cells but did not significantly affect cell migration.

Conclusions

The transcription of NTF3 was lower in HCC samples compared to normal samples, indicating a potential association with disease-free survival and overall survival in HCC. NTF3 and TrkC expression levels were lower in HCC tissues than those in para-cancerous tissues. Our results indicate that NTF3 may be a prognostic factor for HCC.

Keywords:

• Hepatocellular carcinoma
• neurotrophin-3
• tropomyosin-related kinase C
• prognosis
• HCC cell lines

Acknowledgments

We acknowledge all other studies that support our work that were not cited due to length constraints. We would like to thank the funding body that allowed us to carry out this study.

Ethical approval

In vivo study was carried out according to institutional guidelines and experimental procedures approved by the Second Affiliated Hospital, Zhejiang University School of Medicine.

Author contributions

YY, XF, and HW contributed to project design and manuscript drafting. HW and CZ took part in the IHC in tissue microarray. The experiments of cells were accomplished by HW and XF. XF and YY have contributed significantly in drafting the manuscript, literature review and revising it critically. All authors read and approved the final manuscript.

Disclosure statement

The authors declare that they have no conflicts of interest.

Additional information

Funding

This work was supported by the Provincial Key R&D Program of Zhejiang Province (Grant number 2021C03125); and the National Natural Science Foundation of China (Grant number 81872481).