Human cytomegalovirus-induced immune regulation is correlated with poor prognosis in patients with colorectal cancer

Clin Exp Med. 2023 Jun;23(2):427-436. doi: 10.1007/s10238-022-00815-2. Epub 2022 Apr 18.

Abstract

Evidence suggests that human cytomegalovirus (HCMV) infection may be implicated in the progression of colorectal cancer (CRC). However, the correlation between HCMV infection and survival outcomes in patients with CRC remains unclear. Here, we constructed a flow algorithm to identify HCMV sequences based on the RNA-seq data of patients with CRC derived from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The patients' clinical information matrix was used to calculate the Euclidean distance to filter out suitable patients not infected with HCMV, combined with patients' survival outcomes, to reveal how HCMV infection is involved in CRC progression. HCMV infection is widespread in patients with CRC, and the prevalence of HCMV infection ranges from 10 to 36% in four independent CRC datasets, with infection being concentrated in carcinoma tissue rather than in normal tissue. In addition, HCMV-positive patients had a poor survival prognosis, with three HCMV genes, UL82, UL42, and UL117, associated with poor patient survival outcomes. Most importantly, we suppose that the regulation of immune function by HCMV may be key to the poor prognosis of patients with CRC. We found that HCMV infection was associated with poor prognosis in CRC patients and identified three prognosis-associated HCMV genes. The regulation of immune function caused by HCMV infection was the key factor, while HCMV-positive patients with CRC mostly presented with a state of immunosuppression. This may provide new ideas for the personalized treatment of patients with CRC, especially with respect to immunotherapy.

Keywords: Colorectal cancer; Human cytomegalovirus; Immune; Immune checkpoint; Immune infiltration.

MeSH terms

  • Colorectal Neoplasms* / genetics
  • Cytomegalovirus / genetics
  • Cytomegalovirus Infections* / complications
  • Cytomegalovirus Infections* / pathology
  • Humans
  • Prognosis