title: Tumoral presence of human cytomegalovirus is associated with shorter disease-free survival in elderly patients with colorectal cancer and higher levels of intratumoral interleukin-17.
abstract: Infectious diseases are closely related to cancer. Human cytomegalovirus (HCMV) has been implicated in the promotion of tumour growth, and is present in the tumour specimens of colorectal cancer (CRC). This study aimed to investigate whether tumoral presence of HCMV is associated with a different clinical outcome in elderly patients with CRC. We analysed archived tumour specimens from 95 CRC patients aged ≥65 years. HCMV was detected by PCR. Clinical, pathological, disease-free and overall survival data were compared between patients with HCMV-positive and HCMV-negative tumours. A quantitative RT-PCR array was used to evaluate the expression levels of cytokines genes of T-helper subpopulations in tumours. In the Kaplan-Meier analysis of the 81 patients who underwent curative surgery, 39 patients with HCMV-positive tumours had a lower disease-free survival rate (p 0.024). For patients with stage II or stage III tumours, tumoral HCMV status correlated with disease-free survival more closely than the traditional histopathological staging methods. In a multivariate Cox proportional hazard model, tumoral presence of HCMV independently predicted tumour recurrence in 5 years (hazard ratio 4.42; 95% CI 1.54-12.69, p 0.006). The qRT-PCR analysis of ten stage II tumours showed that the gene expression levels of interleukin-17-the signature cytokine of T-helper 17 cells-and its receptor, interleukin-17 receptor C, were higher in the five HCMV-positive tumours. Our results suggest that the presence of HCMV in CRC is associated with poorer outcome in elderly patients. How the virus interacts with the tumour microenvironment should be further investigated.
authors.affiliation: Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: H-P
authors.initials: HP
authors.lastname: Chen
authors.forename: J-K
authors.initials: JK
authors.lastname: Jiang
authors.forename: P-Y
authors.initials: PY
authors.lastname: Lai
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chen
authors.forename: T-Y
authors.initials: TY
authors.lastname: Chou
authors.forename: Y-C
authors.initials: YC
authors.lastname: Chen
authors.forename: C-H
authors.initials: CH
authors.lastname: Chan
authors.forename: S-F
authors.initials: SF
authors.lastname: Lin
authors.forename: C-Y
authors.initials: CY
authors.lastname: Yang
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chen
authors.forename: C-H
authors.initials: CH
authors.lastname: Lin
authors.forename: J-K
authors.initials: JK
authors.lastname: Lin
authors.forename: D M-T
authors.initials: DM
authors.lastname: Ho
authors.forename: W-L
authors.initials: WL
authors.lastname: Cho
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Chan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000150:complications* / Q000401:mortality* / Q000473:pathology; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020381:Interleukin-17 / Q000032:analysis*; D008297:Male; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D020381:Interleukin-17
keywords: Colorectal cancer; T-cell; human cytomegalovirus; malignancy; survival