Genetic polymorphisms of the human cytomegalovirus UL144 gene in colorectal cancer and its association with clinical outcome.
J Gen Virol
; 96(12): 3613-3623, 2015 Dec.
Article
in En
| MEDLINE
| ID: mdl-26450180
ABSTRACT
Human cytomegalovirus (HCMV) has been increasingly detected in colorectal cancer (CRC), and genetic polymorphisms in HCMV affect its pathogenesis. This study aimed to investigate HCMV genetic polymorphisms in CRC and its correlation with the clinical outcomes. We performed PCR and sequencing of a viral immunomodulatory gene, UL144, in clinical isolates and CRC specimens. The nucleotide and amino acid sequences were aligned, and a phylogenetic tree was constructed. The clinical, pathological and survival data were compared among tumours with different UL144 genotypes. HCMV was detected in 49 (47.8 %) of the tumour specimens. Genotype A predominated in 43 samples (22/43; 51.2 %) with successful sequencing, followed by genotype B (13/43; 30.2 %) and genotype C (8/43; 18.6 %). The genotypic distribution was similar to that of the clinical isolates and those reported in other Asian populations. The amino acid sequence of genotype B was the most conserved. For stage II and III CRC patients with HCMV-positive tumours, disease-free survival (DFS) varied among the three major genotypes (P50.0046). The presence of genotype B virus in the tumours was associated with a shorter DFS and independently predicted tumour recurrence in a multivariate Cox proportional hazards model (hazard ratio, 5.79; 95 % confidence interval, 1.3025.81; P50.021). By reverse transcription PCR, tumour samples with genotype B viruses had the highest rate of UL144 expression. Our results suggest that genetic polymorphisms of HCMV UL144 are associated with clinical outcome in CRC and that HCMV may play an immunomodulatory role in the tumour microenvironment of CRC.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
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Viral Proteins
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Membrane Glycoproteins
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Colorectal Neoplasms
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Cytomegalovirus
Type of study:
Prognostic_studies
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Risk_factors_studies
Limits:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
J Gen Virol
Year:
2015
Document type:
Article
Affiliation country: