The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China.
Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, China.
Biomed Res Int. 2020 Mar 17;2020:5201587. doi: 10.1155/2020/5201587. eCollection 2020.
Human papillomavirus (HPV) antigens had been found in colorectal cancer (CRC) tissue, but little evidence demonstrates the association of HPV with oncogene mutations in CRC. We aim to elucidate the mutated genes that link HPV infection and CRC carcinogenesis.
Cancerous and adjacent noncancerous tissues were obtained from CRC patients. HPV antigen was measured by using the immunohistochemical (IHC) technique. The differentially expressed genes (DEGs) in HPV-positive and HPV-negative tumor tissues were measured by using TaqMan Array Plates. The target genes were validated with the qPCR method.
15 (31.9%) cases of CRC patients were observed to be HPV positive, in which HPV antigen was expressed in most tumor tissues rather than in adjacent noncancerous tissues. With TaqMan Array Plates analyses, we found that 39 differentially expressed genes (DEGs) were upregulated, while 17 DEGs were downregulated in HPV-positive CRC tissues compared with HPV-negative tissues. Four DEGs (MMP-7, MYC, WNT-5A, and AXIN2) were upregulated in tumor vs. normal tissues, or adenoma vs. normal tissue in TCGA, which was overlapped with our data. In the confirmation test, MMP-7, MYC, WNT-5A, and AXIN2 were upregulated in cancerous tissue compared with adjacent noncancerous tissue. MYC, WNT-5A, and AXIN2 were shown to be upregulated in HPV-positive CRC tissues when compared to HPV-negative tissues.
HPV-encoding genome may integrate into the tumor genomes that involved in multiple signaling pathways. Further genomic and proteomic investigation is necessary for obtaining a more comprehensive knowledge of signaling pathways associated with the CRC carcinogenesis.
已在结直肠癌（CRC）组织中发现人乳头瘤病毒（HPV）抗原，但几乎没有证据表明 HPV 与 CRC 中的癌基因突变有关。我们旨在阐明将 HPV 感染与 CRC 癌变联系起来的突变基因。
从 CRC 患者中获取癌组织和相邻非癌组织。使用免疫组织化学（IHC）技术测量 HPV 抗原。使用 TaqMan 阵列板测量 HPV 阳性和 HPV 阴性肿瘤组织中的差异表达基因（DEGs）。使用 qPCR 方法验证靶基因。
15 例（31.9%）CRC 患者被观察到 HPV 阳性，其中 HPV 抗原在大多数肿瘤组织中表达，而在相邻非癌组织中不表达。通过 TaqMan 阵列板分析，我们发现与 HPV 阴性组织相比，HPV 阳性 CRC 组织中有 39 个差异表达基因（DEGs）上调，17 个下调。在 TCGA 中，与正常组织相比，4 个 DEGs（MMP-7、MYC、WNT-5A 和 AXIN2）在肿瘤中上调，与我们的数据重叠。在确认试验中，与相邻非癌组织相比，癌组织中 MMP-7、MYC、WNT-5A 和 AXIN2 上调。与 HPV 阴性组织相比，MYC、WNT-5A 和 AXIN2 在 HPV 阳性 CRC 组织中上调。
HPV 编码基因组可能整合到涉及多个信号通路的肿瘤基因组中。进一步的基因组和蛋白质组学研究对于获得与 CRC 癌变相关的信号通路的更全面知识是必要的。
