Expression and prognostic impact of NTF3 and TrkC in hepatocellular carcinoma

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).

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.

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.

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.