Meng Hong-Xue, Yang Xin-Xin, Liu Rui-Qi, Bao Jun-Jie, Hou Yun-Jing, Sun Ji, Miao Su-Sheng, Qu Guo-Fan
Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, People's Republic of China.
Department of Pathology, Harbin Medical University, Harbin, People's Republic of China.
Pharmgenomics Pers Med. 2020 Nov 17;13:633-644. doi: 10.2147/PGPM.S271735. eCollection 2020.
Infection with human papillomavirus (HPV) has been indicated to be a important risk factor for oropharyngeal squamous cell carcinoma (OPSCC). Primary ciliogenesis defects contribute to tumorigenesis, and OFD1 at centriolar satellites is a crucial suppressor of primary ciliogenesis. To identify novel markers associated with HPV-induced carcinogenesis, the interactions between HPV infection and primary ciliogenesis in the tumorigenesis and progression of OPSCC were investigated in this study.
The 1530 OPSCC patients recruited in this research were treated from 2000 to 2017. Immunohistochemistry and RT-PCR were performed on tissue samples to compare the expression of p16, TSLP, TGFβ1, IFNγ, OFD1, and their relationship with clinical characteristics of patients.
We speculate that the positive expression of p16 is related to early primary OPSCC, and the survival rate of p16 positive patients after radiotherapy and surgery is higher. Expression of TSLP on dendritic cells in HPV-positive OPSCC correlated with the expression of OFD1. HPV-positive OPSCC showed increased expression of OFD1 combined with reduced ciliogenesis. Hence, TSLP induced by HPV infection may reduce the invasive potential of OPSCC cells by promoting OFD1 expression, thereby inhibiting primary ciliogenesis.
Our study demonstrated that HPV may be related to the progression of OPSCC by regulating OFD1 expression and primary ciliogenesis, making this protein a potential therapeutic target.
人乳头瘤病毒(HPV)感染已被表明是口咽鳞状细胞癌(OPSCC)的一个重要危险因素。原发性纤毛发生缺陷有助于肿瘤发生,中心粒卫星上的OFD1是原发性纤毛发生的关键抑制因子。为了鉴定与HPV诱导的致癌作用相关的新标志物,本研究调查了HPV感染与原发性纤毛发生在OPSCC肿瘤发生和进展中的相互作用。
本研究招募的1530例OPSCC患者于2000年至2017年接受治疗。对组织样本进行免疫组织化学和逆转录聚合酶链反应,以比较p16、TSLP、TGFβ1、IFNγ、OFD1的表达及其与患者临床特征的关系。
我们推测p16的阳性表达与早期原发性OPSCC有关,放疗和手术后p16阳性患者的生存率更高。HPV阳性OPSCC中树突状细胞上TSLP的表达与OFD1的表达相关。HPV阳性OPSCC显示OFD1表达增加并伴有纤毛发生减少。因此,HPV感染诱导的TSLP可能通过促进OFD1表达来降低OPSCC细胞的侵袭潜能,从而抑制原发性纤毛发生。
我们的研究表明,HPV可能通过调节OFD1表达和原发性纤毛发生与OPSCC的进展相关,使该蛋白成为一个潜在的治疗靶点。