Genetic polymorphisms of the human cytomegalovirus UL144 gene in colorectal cancer and its association with clinical outcome
Autor: | Jeng Kai Jiang, Chia Hao Chan, Chi Hung Lin, Yu Jiun Chan, Teh Ying Chou, Chih Yung Yang, Yen Chung Chen, Hsin Pai Chen, Wan Huai Teo |
---|---|
Rok vydání: | 2015 |
Předmět: |
Male
Human cytomegalovirus Oncology medicine.medical_specialty Genotype Colorectal cancer Cytomegalovirus Biology Disease-Free Survival Virus Viral Proteins Virology Internal medicine medicine Humans Promoter Regions Genetic Gene Phylogeny Aged Aged 80 and over Genetics Membrane Glycoproteins Polymorphism Genetic Reverse Transcriptase Polymerase Chain Reaction Proportional hazards model Hazard ratio Age Factors Middle Aged medicine.disease Reverse transcription polymerase chain reaction DNA Viral Female Colorectal Neoplasms Sequence Alignment |
Zdroj: | Journal of General Virology. 96:3613-3623 |
ISSN: | 1465-2099 0022-1317 |
Popis: | 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 (P = 0.0046). 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, 1.30–25.81; P = 0.021). 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. |
Databáze: | OpenAIRE |
Externí odkaz: |