Esmailzadeh Nadia, Ranaee Mohammad, Alizadeh Ahad, Khademian Aynaz, Saber Amoli Saghar, Sadeghi Farzin
Department of Microbiology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Department of Pathology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.
Gastrointest Tumors. 2020 Apr;7(1-2):30-40. doi: 10.1159/000504293. Epub 2019 Nov 18.
Despite decades of epidemiologic and histopathologic investigations, the association between JC polyomavirus (JCPyV) infection and colorectal cancer (CRC) remains controversial.
This study tested the presence of JCPyV sequences and determined the viral load in a series of colorectal samples from Iranian patients. In total, 223 formalin-fixed paraffin-embedded samples from patients diagnosed with primary and metastatic CRC as well as with nonneoplastic inflamed colon mucosa were analyzed by quantitative real-time PCR for the presence of JCPyV large tumor antigen (LT-Ag) sequences.
JCPyV LT-Ag sequences were detected in 18.6% of the CRC tissues and in 15.5% of the nonneoplastic control group. Viral LT-Ag was quantified in 18/100 primary colon adenocarcinomas, 2/10 metastatic adenocarcinomas, and 1/3 primary adenocarcinomas of the rectum. Two JCPyV-positive metastatic tumors presented a negative test result for JCPyV in the corresponding primary tumor. The median JCPyV LT-Ag copy number was 64 × 10 per cell and 14 × 10 per cell in the CRC cases and the nonneoplastic samples, respectively. There was no statistically significant difference between the two study groups regarding median LT-Ag DNA load ( = 0.059). Among the JCPyV-positive samples, the LT-Ag DNA load was higher in 2 metastatic tumors (from a patient with lung metastasis: 232 × 10 copies per cell; from a patient with liver metastasis: 121 × 10 copies per cell).
The detection of JCPyV DNA at low copy numbers (lower than 1 viral copy per cell equivalent) and the absence of viral sequences in the corresponding primary tumors of the JCPyV-positive metastatic samples weaken the hypothesis of an etiological role of JCPyV in primary CRC induction.
尽管进行了数十年的流行病学和组织病理学研究，但JC多瘤病毒（JCPyV）感染与结直肠癌（CRC）之间的关联仍存在争议。
本研究检测了一系列来自伊朗患者的结直肠样本中JCPyV序列的存在情况，并确定了病毒载量。通过定量实时PCR分析了总共223份来自诊断为原发性和转移性CRC以及非肿瘤性炎症性结肠黏膜患者的福尔马林固定石蜡包埋样本中JCPyV大肿瘤抗原（LT-Ag）序列的存在情况。
在18.6%的CRC组织和15.5%的非肿瘤对照组中检测到JCPyV LT-Ag序列。在100例原发性结肠腺癌中的18例、10例转移性腺癌中的2例以及直肠原发性腺癌中的1例中对病毒LT-Ag进行了定量。两个JCPyV阳性转移性肿瘤在相应的原发性肿瘤中JCPyV检测结果为阴性。CRC病例和非肿瘤样本中JCPyV LT-Ag的中位数拷贝数分别为每细胞64×10和每细胞14×10。两组之间关于LT-Ag DNA载量中位数无统计学显著差异（P = 0.059）。在JCPyV阳性样本中，2例转移性肿瘤的LT-Ag DNA载量较高（1例肺转移患者：每细胞232×10拷贝；1例肝转移患者：每细胞121×10拷贝）。
在低拷贝数（低于每细胞当量1个病毒拷贝）下检测到JCPyV DNA以及JCPyV阳性转移性样本的相应原发性肿瘤中不存在病毒序列，削弱了JCPyV在原发性CRC诱导中具有病因学作用的假说。
