对结直肠癌患者 JC 病毒重排非编码调控区的新评估。

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

机构信息

Cancer, Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Biostatistics and Epidemiology Department, Health School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

出版信息

BMC Cancer. 2024 Aug 12;24(1):1001. doi: 10.1186/s12885-024-12684-x.

DOI:10.1186/s12885-024-12684-x

PMID:39134946

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11320957/

Abstract

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.

摘要

背景

多项研究报道了 JC 病毒（JCV）在人类肿瘤中的存在。JCV 与 CRC 的关联仍存在争议。本研究旨在评估 CRC 患者组织样本中检测到的 JCV DNA 的重组 NCCR 区。

方法

在这项病例对照研究中，收集了 60 例 CRC 患者的肿瘤组织（n=60）、相邻正常组织（n=60）和尿液样本（n=60）。采用巢式 PCR 检测 JCV 基因组的 VP1 和 NCCR 区。对阳性 JCV PCR 产物进行测序，并构建系统发育树以确定 JCV 基因型。提取 RNA 并制备 cDNA 后，在 60 个肿瘤组织和 60 个相邻正常组织中检测 JCV LTAg 的表达。使用 GraphPad Prism 软件版本 8 分析 JCV LTAg 表达。

结果

分析显示，35/60（58.3%）肿瘤组织中检测到 JCV DNA，而 36/60（60.0%）相邻正常组织中检测到 JCV DNA（p=0.85）。与 60 例 CRC 患者的 35/60（58.3%）肿瘤组织相比，42/60（70.0%）尿液样本中检测到 JCV DNA，但差异无统计学意义（P=0.25）。系统发育树分析显示，优势 JCV 基因型为 3，其次是基因型 2D，分布于 CRC 患者的肿瘤组织、正常组织和尿液样本中。对来自肿瘤组织样本 JCV 区域的随机选择的 NCCR 序列进行分析，显示存在不同长度的重组 NCCR 块：431 bp、292 bp、449 bp 和 356 bp。这些重组的 NCCR 块与 PML 型 Mad-1、Mad-4、Mad-7 和 Mad-8 原型中描述的重组 NCCR 块不同。JCV LTAg 的表达在肿瘤组织中与正常组织相比有显著差异，p 值小于 0.002。

结论

35%>CRC 患者的肿瘤组织和尿液样本中发现 JCV DNA 呈阳性（P=0.25）。对肿瘤和尿液样本中 JCV DNA 的平行分析进一步支持潜在的非侵入性筛查工具。本研究为 CRC 患者提供了对来自患者的重组 NCCR 变异体分离物的新见解。JCV LTAg 在肿瘤组织和正常组织之间的表达差异表明潜在的 JCV 状态可能导致癌症发展。