Down-regulation of TRPV6 Is Associated With Adverse Prognosis in Hepatocellular Carcinoma Treated With Curative Resection

Cancer Genomics Proteomics. 2022 Mar-Apr;19(2):259-269. doi: 10.21873/cgp.20318.

Abstract

Background/aim: Transient receptor potential vanilloid 6 (TRPV6), an endothelial Ca2+-selective entry channel, is expressed in various cancer types, and a selective TRPV6 inhibitor is currently being investigated in a clinical trial. However, TRPV6 expression in hepatocellular carcinoma (HCC) has not been reported.

Materials and methods: We evaluated TRPV6 expression in 219 cases of HCC and analyzed its association with clinicopathological parameters and prognostic significance. TRPV6 mRNA expression was compared between HCC and non-tumor liver tissues using various public datasets, and its prognostic effect was examined in The Cancer Genome Atlas (TCGA) cohort.

Results: Low TRPV6 expression was found in 37.4% of patients, which was significantly associated with adverse histologic features, and patients with low TRPV6 expression had shorter recurrence-free and disease-free survival. TRPV6 mRNA expression was consistently lower in HCC compared to non-tumor liver samples in public datasets, at the whole tissue level as well as single-cell level. Patients with low TRPV6 expression in the TCGA cohort had shorter progression-free survival.

Conclusion: TRPV6 expression is down-regulated in HCCs and associated with a poor prognosis. TRPV6 may be a prognostic biomarker in HCC.

Keywords: Hepatocellular carcinoma; TRPV6; biomarkers; prognosis; recurrence.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / surgery
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / surgery
  • Prognosis
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism

Substances

  • Biomarkers, Tumor
  • Calcium Channels
  • TRPV Cation Channels
  • TRPV6 protein, human