Journal Article

A new evaluation of the rearranged non-coding control region of JC virus in patients with colorectal cancer

Haghi Navand, Azadeh, Karimi Babaahmadi, Mohammad, Makvandi, Manoochehr, Ahmadi Angali, Kambiz, Talaiezadeh, Abdolhassan, Jalilian, Shahram

2024

Overview

Highlights A significant proportion of 35/60 (58.33%) tumor tissue and 42/60 (70%) urine samples of the CRC patients were found to be positive for JCV DNA ( P  = 0.25). The parallel analysis of tumor and urine samples for JCV DNA further supports the potential for non-invasive screening tools. screening JCV DNA in peripheral blood mononuclear cells (PBMCs) and stool of CRC patients may further support the potential for non-invasive screening tools. The study offers new insights into rearranged NCCR variants isolated from colorectal cancer (CRC) patients’ tissue. The screening and analysis of the rrNCCR region of JCV DNA in CRC patients’ stool may indicate the pathogenesis of the JCV virus in CRC development. The presence of JCV LTAg in tumor tissue is significantly higher than in normal tissue (p = < 0.002), suggesting JCV’s role in cancer development during the latency phase. Background Several studies have reported the presence of JC virus (JCV) in human tumors, The association of JCV and CRC remains controversial. This study aimed to evaluate the rearranged NCCR region of the detected JCV DNA in CRC patients’ tissue samples. Methods In this case-control study, tumor tissues ( n  = 60), adjacent normal tissues ( n  = 60), and urine samples ( n  = 60) of the CRC patients were collected. The nested PCR was employed to detect the VP1 and NCCR regions of the JCV genome. The positive JCV PCR products were sequenced and a phylogenetic tree was constructed to determine the JCV genotypes. After extracting RNA and preparing cDNA, the expression of JCV LTAg was examined in 60 tumor tissues and 60 adjacent normal tissues. The analysis of JCV LTAg expression was performed using GraphPad Prism software version 8. Results The analysis reveals that JCV DNA was detected in 35/60 (58.3%) tumor tissues, while 36/60 (60.0%) of adjacent normal tissues ( p  = 0.85). JCV DNA was detected in 42/60 (70.0%) urine samples when compared to 35/60 (58.3%) tumor tissues of CRC patients and was not found significant ( P  = 0.25). The phylogenetic tree analysis showed the dominant JCV genotype 3, followed by genotype 2D was distributed in tumor tissue, normal tissue, and urine samples of the CRC patients. Analysis of randomly selected NCCR sequences from JCV regions in tumor tissue samples revealed the presence of rearranged NCCR blocks of different lengths.: 431 bp, 292 bp, 449 bp, and 356 bp. These rearranged NCCR blocks differ from the rearranged NCCR blocks described in PML-type Mad-1, Mad-4, Mad-7, and Mad-8 prototypes. The expression of JCV LTAg was significantly different in tumor tissue compared to normal tissue, with a p-value of less than 0.002. Conclusion A significant proportion of 35%> of the tumor tissue and urine samples of the CRC patients was found to be positive for JCV DNA ( P  = 0.25). The parallel analysis of tumor and urine samples for JCV DNA further supports the potential for non-invasive screening tools. This study provides new insights into Rearranged NCCR variant isolates from patients with CRC. The significant difference in JCV LTAg expression between tumor and normal tissue indicates a latent JCV status potentially leading to cancer development.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Aged / Aged, 80 and over / Antigens / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer patients / Cancer Research / Cancer therapies / Case-Control Studies / Cell cycle / Colorectal cancer / Colorectal carcinoma / Colorectal neoplasms / Colorectal Neoplasms - genetics / Colorectal Neoplasms - urine / Colorectal Neoplasms - virology / Deoxyribonucleic acid / Development and progression / Diagnosis / DNA / DNA viruses / DNA, Viral - genetics / DNA, Viral - urine / Female / Gene Rearrangement / Genetic aspects / Genomes / Genotype / Genotypes / Health aspects / Health Promotion and Disease Prevention / Humans / Infections / Invasiveness / JC Virus - genetics / JC Virus - isolation & purification / Latency / Leukocytes (mononuclear) / Male / Medicine/Public Health / Middle Aged / Nested polymerase chain reaction, JC virus / Oncology / Oncology, Experimental / Peripheral blood mononuclear cells / Phylogenetics / Phylogeny / Physiological aspects / Polymerase chain reaction / Polyoma virus / Polyomavirus Infections - urine / Polyomavirus Infections - virology / Proteins / Surgical Oncology / Tumor Virus Infections - urine / Tumor Virus Infections - virology / Tumors / Urine / Viruses