Mobaraki Ghalib, Shi Shuai, Smits Kim M, Severens Kim, Lommen Kim, Rennspiess Dorit, Chteinberg Emil, Winnepenninckx Véronique, Samarska Iryna, Klufah Faisal, Hausen Axel Zur
Department of Pathology, GROW-Institute for Oncology & Reproduction, Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands.
Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia.
Cancers (Basel). 2024 Apr 29;16(9):1746. doi: 10.3390/cancers16091746.
Previous studies have indicated a potential role of diet in the pathogenesis of renal cell carcinoma (RCC). Recently, circular bovine meat and milk factor (BMMF) DNAs have been identified in peritumoral tissues of human colon and breast cancers. Here, we investigated the prevalence of the DNA of these novel human pathogenic infectious agents in RCC and adjacent peritumoral renal tissues. DNA was extracted from formalin-fixed and paraffin-embedded (FFPE) RCC and peritumoral kidney tissues, including a test (n = 11) and a validation (n = 152) collection. BMMF1 and BMMF2 consensus primers were designed to screen for the presence of BMMF1- and BMMF2-like DNA. In addition, BMMF-specific PCR was performed on selected cases to test for the presence of additional regions of BMMF1 and BMMF2 genomes. A reference collection of hepatocellular carcinomas (HCCs; n = 60) and adjacent peritumoral liver tissues (n = 50) was also included. Our results demonstrated that BMMF1 and BMMF2 DNAs are frequently found in human RCC tissues and are particularly more prevalent in peritumoral kidney tissues. Of note, BMMF1 and BMMF2 genotype heterogeneity was higher in peritumoral kidney tissues compared to RCC tissues. This is the first study to directly test human FFPE tissues for BMMF1- and BMMF2-like DNA using consensus PCR and demonstrate BMMF DNA in neoplastic and peritumoral kidney tissues. The findings are in line with the recently proposed indirect etiopathogenetic role of BMMFs in, e.g., colorectal carcinogenesis. Follow-up studies are needed to explore the potential role of BMMFs in the etiopathogenesis of RCC.
以往研究表明饮食在肾细胞癌（RCC）发病机制中可能发挥作用。最近，在人类结肠癌和乳腺癌的瘤周组织中发现了环状牛源肉和乳因子（BMMF）DNA。在此，我们调查了这些新型人类致病感染因子的DNA在RCC及相邻瘤周肾组织中的流行情况。从福尔马林固定石蜡包埋（FFPE）的RCC和瘤周肾组织中提取DNA，包括一个测试集（n = 11）和一个验证集（n = 152）。设计BMMF1和BMMF2共有引物以筛查类似BMMF1和BMMF2的DNA的存在。此外，对选定病例进行BMMF特异性PCR，以检测BMMF1和BMMF2基因组其他区域的存在。还纳入了一个肝细胞癌（HCC；n = 60）及相邻瘤周肝组织（n = 50）的参考集。我们的结果表明，BMMF1和BMMF2 DNA在人类RCC组织中经常被发现，并且在瘤周肾组织中尤为普遍。值得注意的是，与RCC组织相比，瘤周肾组织中BMMF1和BMMF2基因型的异质性更高。这是第一项使用共有PCR直接检测人类FFPE组织中类似BMMF1和BMMF2的DNA并在肿瘤性和瘤周肾组织中证实BMMF DNA的研究。这些发现与最近提出的BMMF在例如结直肠癌发生中的间接病因学作用一致。需要进行后续研究以探索BMMF在RCC病因学中的潜在作用。
