Abstract
BackgroundJCV is a DNA polyomavirus very well adapted to humans. Although JCV DNA has been detected in colorectal cancers (CRC), the association between JCV and CRC remains controversial. In China, the presence of JCV infection in CRC patients has not been reported. Here, we investigated JCV infection and viral DNA load in Chinese CRC patients and to determine whether the JCV DNA in peripheral blood (PB) can be used as a diagnostic marker for JCV-related CRC.Methodology/Principal FindingsTumor tissues, non-cancerous tumor-adjacent tissues and PB samples were collected from 137 CRC patients. In addition, 80 normal colorectal tissue samples from patients without CRC and PB samples from 100 healthy volunteers were also harvested as controls. JCV DNA was detected by nested PCR and glass slide-based dot blotting. Viral DNA load of positive samples were determined by quantitative real-time PCR. JCV DNA was detected in 40.9% (56/137) of CRC tissues at a viral load of 49.1 to 10.3×104 copies/µg DNA. Thirty-four (24.5%) non-cancerous colorectal tissues (192.9 to 4.4×103 copies/µg DNA) and 25 (18.2%) PB samples (81.3 to 4.9×103 copies/µg DNA) from CRC patients were positive for JCV. Tumor tissues had higher levels of JCV than non-cancerous tissues (P = 0.003) or PB samples (P<0.001). No correlation between the presence of JCV and demographic or medical characteristics was observed. The JCV prevalence in PB samples was significantly associated with the JCV status in tissue samples (P<0.001). Eleven (13.8%) normal colorectal tissues and seven (7.0%) PB samples from healthy donors were positive for JCV.Conclusions/SignificanceJCV infection is frequently present in colorectal tumor tissues of CRC patients. Although the association between JCV presence in PB samples and JCV status in tissue samples was identified in this study, whether PB JCV detection can serve as a marker for JCV status of CRC requires further study.
Highlights
The John Cunningham virus (JCV) is a ubiquitous, small, nonenveloped polyomavirus with a closed, circular, double-stranded DNA genome that frequently resides in the kidneys of healthy individuals and is excreted in the urine of a large portion of the adult population
We found both matched pairs of tumor tissue and non-cancerous tissue from 17.5% (24 of 137) of colorectal cancers (CRC) patients were positive for JCV DNA. 23.4% (32 of 137) and 7.3% (10 of 137) of patients had JCV DNA only in tumor tissue or non-cancerous tumor-adjacent tissue, respectively (Figure 1C). 18.2% (25 of 137) of peripheral blood (PB) samples from CRC patients were positive for JCV DNA
A significantly higher JCV presence was observed in CRC tissues compared with non-cancerous adjacent tissues (OR, 2.089; 95% CI, 1.213–3.636; P = 0.007) and PB samples (OR, 3.084; 95% CI, 1.729–5.619; P,0.001)
Summary
The John Cunningham virus (JCV) is a ubiquitous, small, nonenveloped polyomavirus with a closed, circular, double-stranded DNA genome that frequently resides in the kidneys of healthy individuals and is excreted in the urine of a large portion of the adult population. JCV genomic DNA sequences and T-antigen expression have been detected in a broad range of human tumor cell types including oligodendrocytes, astrocytomas, glioblastomas, ependymomas, and most other types of brain tumors [8], indicating that JCV infection may be associated with human carcinogenesis. JCV infection was first reported as a potential risk factor for colorectal cancer (CRC) in a work by Laghi et al [11], which found that 96% of CRC tissues were positive for JCV DNA sequences. Other studies have subsequently shown that no detectable JCV DNA was present in colorectal tissues indicating no association between JCV and colon neoplasia [16,17]. We investigated JCV infection and viral DNA load in Chinese CRC patients and to determine whether the JCV DNA in peripheral blood (PB) can be used as a diagnostic marker for JCV-related CRC
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