HAVCR1 expression might be a novel prognostic factor for gastric cancer

PLoS One. 2018 Nov 2;13(11):e0206423. doi: 10.1371/journal.pone.0206423. eCollection 2018.


Hepatitis A virus cellular receptor 1 (HAVCR1), which is also known as T-cell immunoglobulin and mucin domain 1 (TIM-1) is a TIM gene family member. In this study, we aimed to characterize the expression profile of HAVCR1 in GC, its prognostic value and the potential epigenetic mechanism leading to its dysregulation. Bioinformatic analysis was performed by using genomic, clinicopathological and survival data in the human protein atlas (HPA) and the Cancer Genome Atlas (TCGA). Results showed that HAVCR1 was significantly upregulated at the mRNA and protein level in GC tissues compared to the adjacent normal tissues. In addition, HAVCR1 upregulation was an independent indicator of shorter OS (HR: 1.698, 95%CI: 1.221-2.361, p = 0.002), after adjustment of older age, differentiation status, pathological stages and the presence of residual tumor and was also an independent indicator of shorter RFS (HR: 2.577, 95%CI: 1.583-4.197, p<0.001), after adjustment of gender and histological grade. The methylation level of two CpG sites (cg11188031 and cg07320595) was negatively correlated with HAVCR1 expression. However, only high methylation level of cg07320595 was associated with significantly longer OS (p = 0.018) and RFS (p = 0.021). Based on these findings, we infer that HAVCR1 upregulation might serve as a valuable prognostic marker in terms of OS and RFS in GC patients. Cg07320595 might be a critical CpG site influencing HAVCR1 expression.

MeSH terms

  • Aged
  • Computational Biology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Hepatitis A Virus Cellular Receptor 1 / genetics*
  • Hepatitis A Virus Cellular Receptor 1 / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / therapy
  • Survival Analysis
  • Treatment Outcome


  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • RNA, Messenger

Grants and funding

The author(s) received no specific funding for this work.