Serological and viraemic status of human cytomegalovirus infection in patients with colorectal cancer is not correlated with viral replication and transcription in tumours

Abstract

Colorectal cancer (CRC) is amongst the leading causes of cancer-related mortality worldwide. Emerging evidence suggests that human cytomegalovirus (HCMV) exists in the tumour tissue of CRC and is associated with disease outcome. To study whether tumoral HCMV is related to viral reactivation in blood, tumour specimens and pre-and post-operative blood samples from CRC patients were collected prospectively. PCR and quantitative PCR were performed to detect HCMV DNA. HCMV IgG and IgM antibodies were measured using a microparticle enzyme immunoassay. Transcription of a spliced HCMV UL73 gene transcript was analysed by quantitative reverse transcription PCR. HCMV was detected in 42.2 % (35/83) of the tumour samples, with a low median viral load (30.08, range 2.33-5704 copies per 500 ng genomic DNA). The vast majority (80/81, 98.8 %) of the CRC patients were seropositive for HCMV IgG. HCMV DNA was positive in 11.3 % (22/194) of the pre-operative and 8.9 % (15/168) of the post-operative blood samples. However, presence of HCMV and its viral load in tumours were not associated with the detection or viral loads in blood samples. About 26.67 % (8/30) of the HCMV-positive tumours with available RNA had detectable viral UL73 transcripts, whilst none of the blood samples were positive for viral RNA (P,0.0001). Therefore, presence of HCMV in tumours does not correlate with the serological or viraemic status of CRC patients. Active viral gene transcription occurred in the tumour but not in the blood of CRC patients. HCMV reactivation in CRC patients is possibly due to virus-cancer interactions in the CRC tumour microenvironment.

Human cytomegalovirus infection and colorectal cancer risk: a meta-analysis

“…We found that there was a certain prevalence of HCMV DNA (28.7%) in CRC tissues, compared to a high rate of HCMV detection (over 80%) in patients’ plasma [16, 21]. Some reports attributed low or negative detection to the type of sample.…”

“…Inadequate data has been obtained to confirm the causal role of HCMV in carcinogenesis processes, tumor progression and metastasis [19]. Although HCMV infection is considered to have relationship with CRC, the clinical and pathological features of patients are also various [20, 21]. …”

Detection of human cytomegalovirus in glioblastoma among Taiwanese subjects

“…Its sensitivity was better than that for detecting HCMV US28 gene (S1 Table). Our colleagues from our department had detected HCMV UL73 gene in 42.2% (35/83) of the colorectal tumor samples [36] and shown good correlation with the result of PCR for HCMV UL55 in 23 pairs of colorectal cancer and adjacent non-neoplastic specimen [33]. In regard to the age of the specimen, Ranganathan et al had demonstrated that detecting HCMV UL144 gene in GBMs was more sensitive than detecting UL28 and UL55, especially for older formalin-fixed, paraffin-embedded (FFPE) samples [37].…”

Identification of human cytomegalovirus in tumour tissues of colorectal cancer and its association with the outcome of non-elderly patients

“…Whether such Based on the results of this study and our previous work that compared the viral loads in tumour and normal specimens of CRC (Chen et al, 2012), we speculate that HCMV directly infects, or reactivates within, the neoplastic epithelium of CRC. Virus replication possibly correlated with changes in the tumour microenvironment, since the serologic and viraemic status of HCMV is not associated with viral replication and transcription in tumour tissues (Chen et al, 2016). Furthermore, since the ISH probe targeted the most abundantly transcribed viral gene during permissive infection (McSharry et al, 2003;Wu et al, 1992), the virus is probably not 'dormant' in tumours of CRC.…”