Chuerduangphui Jureeporn, Pientong Chamsai, Patarapadungkit Natcha, Chotiyano Apinya, Vatanasapt Patravoot, Kongyingyoes Bunkerd, Promthet Supannee, Swangphon Piyawut, Bumrungthai Sureewan, Pimson Charinya, Ekalaksananan Tipaya
Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
Med Oncol. 2017 Sep;34(9):148. doi: 10.1007/s12032-017-1010-6. Epub 2017 Jul 24.
Human papillomavirus (HPV) infection is associated with several genetic alterations including oncogene amplification, leading to increased aggression of tumors. Recently, a relationship between HPV infection and oncogene amplification has been reported, but this finding remains controversial. This study therefore investigated relationships between HPV infection and amplification of genes in the epidermal growth factor receptor (EGFR) signaling cascade in oral squamous cell carcinoma (OSCC). Extracted DNA from 142 formalin-fixed paraffin-embedded (FFPE) OSCC tissues was performed to investigate the copy number of EGFR, KRAS, c-myc and cyclin D1 genes using real-time polymerase chain reaction (RT-PCR) and compared with calibrators. A tissue microarray of OSCC tissues was used for detection of c-Myc expression and HPV infection by immunohistochemistry and HPV E6/E7 RNA in situ hybridization, respectively. HPV infection was also investigated using PCR and RT-PCR. Of the 142 OSCC samples, 81 (57%) were HPV-infected cases. The most frequently amplified gene was c-myc (55.6%), followed by cyclin D1 (26.1%), EGFR (23.9%) and KRAS (19.7%). Amplification of c-myc was significantly associated with levels of its protein product. EGFR amplification was also significantly associated with amplification of genes in the signaling cascade: KRAS (50.0%), c-myc (34.2%) and cyclin D1 (46.0%). Interestingly, HPV infection was significantly associated with amplification of both EGFR (76.5%) and cyclin D1 (73.0%). Only cyclin D1 amplification was significantly associated with severity of OSCC histopathology. HPV infection may play an important synergistic role in amplification of genes in the EGFR signaling cascade, leading to increased aggression in oral malignancies.
人乳头瘤病毒（HPV）感染与多种基因改变相关，包括癌基因扩增，这会导致肿瘤侵袭性增强。最近，有报道称HPV感染与癌基因扩增之间存在关联，但这一发现仍存在争议。因此，本研究调查了口腔鳞状细胞癌（OSCC）中HPV感染与表皮生长因子受体（EGFR）信号级联反应中基因扩增之间的关系。使用实时聚合酶链反应（RT-PCR）对142例福尔马林固定石蜡包埋（FFPE）的OSCC组织提取的DNA进行检测，以研究EGFR、KRAS、c-myc和细胞周期蛋白D1基因的拷贝数，并与校准物进行比较。分别使用免疫组织化学和HPV E6/E7 RNA原位杂交技术，对OSCC组织的组织芯片进行c-Myc表达检测和HPV感染检测。还使用PCR和RT-PCR对HPV感染进行了研究。在142例OSCC样本中，81例（57%）为HPV感染病例。最常扩增的基因是c-myc（55.6%），其次是细胞周期蛋白D1（26.1%）、EGFR（23.9%）和KRAS（19.7%）。c-myc的扩增与其蛋白产物水平显著相关。EGFR扩增也与信号级联反应中的基因扩增显著相关：KRAS（50.0%）、c-myc（34.2%）和细胞周期蛋白D1（46.0%）。有趣的是，HPV感染与EGFR（76.5%）和细胞周期蛋白D1（73.0%）的扩增均显著相关。只有细胞周期蛋白D1扩增与OSCC组织病理学严重程度显著相关。HPV感染可能在EGFR信号级联反应中的基因扩增中起重要的协同作用，导致口腔恶性肿瘤的侵袭性增加。
