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 One supplementary table is available with the online Supplementary Material.

The impact of inflationary cytomegalovirus‐specific memory T cells on anti‐tumour immune responses in patients with cancer

“…Additionally, higher transcription of IL‐17 was found in CMV‐positive tumours, which correlates with a poor outcome of CRC . On the contrary, presence of CMV in CRC tumours among patients < 65 years of age independently predicted a higher disease‐free survival rate based on multivariate Cox proportional hazards analysis . In this study, significant intra‐tumoral inflammatory responses were more frequently observed in CMV‐positive tumours with lower levels of IL‐1, a pleiotropic cytokine implicated in promoting tumour growth, angiogenesis and potentially metastasis .…”

“…136,137 On the contrary, presence of CMV in CRC tumours among patients < 65 years of age independently predicted a higher disease-free survival rate based on multivariate Cox proportional hazards analysis. 138 In this study, significant intra-tumoral inflammatory responses were more frequently observed in CMV-positive tumours with lower levels of IL-1, a pleiotropic cytokine implicated in promoting tumour growth, angiogenesis and potentially metastasis. 139,140 Taken together, CMV may enhance immunity to cancer in younger patients whereas longterm CMV infection may be detrimental to clinically relevant anti-tumour immune responses in older individuals ( Fig.…”

Patients with Helicobacter pylori‑positive gastric cancer with human cytomegalovirus infection have a low tendency of advanced lymphatic metastasis in a Chinese population

“…In human malignant glioma, which is the most studied HCMV-associated tumor, HCMV infection is mainly regarded as a tumor promoter (42,43). However, previous studies have revealed that HCMV may be a protective factor in the outcome of gastrointestinal tumors, breast cancer and hepatocellular carcinoma (44)(45)(46)(47). Furthermore, the HCMV genes US28 (48) and UL123 (49) can accelerate tumor growth and enhance cancer cell stemless, while UL138 can promote the apoptosis of cancer cells (17).…”

Cytomegalovirus Infection Is a Risk Factor in Gastrointestinal Cancer: A Cross-Sectional and Meta-Analysis Study

“…The detailed evaluation of the 67 remaining studies resulted in the further exclusion of 57 due to duplicated publications, lack of adequate data, or no original date for the meta-analysis. Finally, 10 publications were included in our meta-analysis [11,[16][17][18][19][20][21][22][23][24]. The study selection process has been depicted as a flow chart in online supplementary Figure 1 (for all online suppl.…”