title: Identification of human cytomegalovirus in tumour tissues of colorectal cancer and its association with the outcome of non-elderly patients.
abstract: Increasing evidence suggests that human cytomegalovirus (HCMV) plays an oncomodulatory role in human cancers. In colorectal cancer (CRC), presence of HCMV in tumours has been associated with a poor outcome in elderly patients. This study aimed to investigate the association between HCMV and the outcome of non-elderly patients with CRC. In tumour samples, HCMV DNA was detected by PCR. Viral transcript and protein were detected by in situ hybridization (ISH) and immunohistochemical staining (IHC), respectively. Clinical, pathological and survival data were compared between patients with HCMV-positive and -negative tumours. Quantitative reverse transcription PCR (qRT-PCR) was used to analyse the expression levels of cellular signals related to CRC progression and metastasis. Among 89 CRC non-elderly patients aged <65 years, HCMV was detected in 31 (34.8 %) tumour samples by PCR. By ISH and IHC, viral transcript and protein specifically localized to the cytoplasm of neoplastic mucosal epithelium. Outcome analysis revealed a more favourable disease-free survival (DFS) rate in patients with HCMV-positive tumours (P<0.01), specifically in patients with stage III disease. In a multivariate Cox proportional-hazard model, tumoural presence of HCMV independently predicted a higher DFS rate (hazard ratio 0.22; 95 % confidence interval 0.075-0.66, P<0.01). By qRT-PCR, the tumoural levels of interleukin-1 were relatively lower in samples positive for HCMV. The results suggest that HCMV may influence the outcome of CRC in an age-dependent manner and possibly has a dual oncomodulatory effect. How the virus interacts with the tumour microenvironment should be further studied.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.|School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.|Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan, ROC.
authors.forename: Hsin-Pai
authors.initials: HP
authors.lastname: Chen
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.|Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Jeng-Kai
authors.initials: JK
authors.lastname: Jiang
authors.affiliation: Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan, ROC.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, ROC.
authors.forename: Chih-Yung
authors.initials: CY
authors.lastname: Yang
authors.affiliation: Department of Pathology, National Yang-Ming University Hospital, Yilan, Taiwan, ROC.
authors.forename: Yen-Chung
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Institute of Microbiology and Immunology, School of Life Science, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.|Division of Molecular Pathology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Teh-Ying
authors.initials: TY
authors.lastname: Chou
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.|Department of Medicine, Mackay Medical College, Taipei, Taiwan, ROC.
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Cho
authors.affiliation: Division of Microbiology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.|Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.|Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Yu-Jiun
authors.initials: YJ
authors.lastname: Chan
mesh_terms: D015179:Colorectal Neoplasms / Q000473:pathology / Q000821:virology*; D003587:Cytomegalovirus / Q000302:isolation & purification*; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D060787:Neoplasm Grading; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome; D014764:Viral Proteins / Q000032:analysis / Q000276:immunology
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral; D014764:Viral Proteins