Ebrahimian Shiadeh Arefeh, Hamidi Sofiani Vahideh, Saber Amoli Saghar, Taheri Mahdie, Tabarraei Alijan, Razavi Nikoo Hadi, Sadeghi Farzin, Khafri Sorayya, Kamrani Ghodsieh, Yahyapour Yousef, Moradi Abdolvahab
Department of Medical Microbiology, Faculty of Medicine, Golestan University of Medical Science, Gorgan, Iran.
Department of Medical Microbiology and Biotechnology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.
Int J Mol Cell Med. 2023;12(3):288-299. doi: 10.22088/IJMCM.BUMS.12.3.288.
Viral infections contribute to 15-20% of newly diagnosed cancers worldwide. There is evidence of a possible etiological role of Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HR-HPVs) in colorectal carcinoma (CRC). Loss of p53 and p16 function has been found in many cancers and this may occur in many different ways, including gene mutation or interaction with viral oncoproteins. This study aimed to evaluate the presence of EBV and HPV in CRC patients in northern Iran and to assess p53 and p16 protein expression related to these viral infections. Real-time PCR was used to amplify the DNA sequences of these viruses in 55 colorectal tumoral tissues, along with their corresponding non-tumoral adjacent tissues. Additionally, immunohistochemistry (IHC) was utilized to determine p53 and p16 protein expression. EBV DNA was detected in 49.1% of CRC tissues. Furthermore, HPV DNA was present in 7.3% of CRC tissues. Notably, the prevalence of EBV infection in tumoral tissues was significantly higher than in non-tumoral tissues (P=0.001). The EBV DNA polymerase catalytic subunit (BALF5) copy number in tumoral tissues was higher than in non-tumoral tissues and this difference was statistically significant (P=0.008). P53 was positive in 21/26 (80.8%) EBV-positive and in 11/25 (44%) EBV-negative samples and this difference was significant (P=0.007). P16 was positive in 13/26 (50%) EBV-positive and in 14/25 (58.3%) EBV-negative samples (P= 0.668). Our findings suggest that EBV infection can increase the risk of CRC. In addition, EBV seems to stabilize p53 in EBV-positive CRC which needs further research. No significant correlation was detected between EBV infection and p16 expression. Also, we could not find a causal relationship between HPV infection and CRC in the study population.
在全球范围内，病毒感染导致15%至20%的新发癌症。有证据表明，爱泼斯坦-巴尔病毒（EBV）和高危型人乳头瘤病毒（HR-HPVs）在结直肠癌（CRC）中可能具有病因学作用。在许多癌症中都发现了p53和p16功能的丧失，这可能通过多种不同方式发生，包括基因突变或与病毒癌蛋白的相互作用。本研究旨在评估伊朗北部CRC患者中EBV和HPV的存在情况，并评估与这些病毒感染相关的p53和p16蛋白表达。采用实时聚合酶链反应（PCR）对55例结直肠肿瘤组织及其相应的非肿瘤相邻组织中的这些病毒的DNA序列进行扩增。此外，利用免疫组织化学（IHC）来确定p53和p16蛋白表达。在49.1%的CRC组织中检测到EBV DNA。此外，7.3%的CRC组织中存在HPV DNA。值得注意的是，肿瘤组织中EBV感染的患病率显著高于非肿瘤组织（P = 0.001）。肿瘤组织中EBV DNA聚合酶催化亚基（BALF5）的拷贝数高于非肿瘤组织，且这种差异具有统计学意义（P = 0.008）。在21/26（80.8%）的EBV阳性样本和11/25（44%）的EBV阴性样本中p53呈阳性，这种差异具有显著性（P = 0.007）。在13/26（50%）的EBV阳性样本和14/25（58.3%）的EBV阴性样本中p16呈阳性（P = 0.668）。我们的研究结果表明，EBV感染会增加CRC的风险。此外，EBV似乎能使EBV阳性的CRC中的p53稳定，这需要进一步研究。未检测到EBV感染与p16表达之间存在显著相关性。而且，在研究人群中我们未发现HPV感染与CRC之间存在因果关系。
