成人上呼吸道乳头状瘤IL-1α3’UTR遗传易感性与HPV感染相互作用机制研究

The incidence of adult upper respiratory papillomatosis was increased along with the HPV infection year by year, but the recurrent rate still remain on 5 to 10%, and some patients also have the trend to malignant transformation. To date, patients who were neoplastic transformation lack of effective early detection. In previous studies we found that the polymorphism of IL-1a3'UTR region (rs3783553) in head and neck squamous cancer cells were multi-functional, and could increase the serum levels of IL-1a and the cancer susceptibility of HPV-positive patients, but the exact interaction mechanism between IL-1a and the HPV virus remain unexplored. Then we try to constructe different genotypes and HPV infection status of cell lines to confirm the expression regulatory rs3783553 polymorphism on IL-1a in vitro, and illustrate the effect of HPV infection on IL-1a and its downstream NFkB signaling pathway, as well as the protein expression regulation of IL-1a to E6, E7, compared the polymorphism of rs3783553 located in IL-1a3'UTR region in malignant patients with preneoplastic transformation, and the relationship between the serum levels of IL-1a and the prognosis, to clarify how IL-1a interact synergistically with HPV in the development of disease progression. It will provide new conceptions and methods for clinical individualized precision medical.

随着HPV感染率增加，成人上呼吸道乳头状瘤发病率逐年增加，在治疗后仍有5-10%复发，且部分患者易恶变。目前对易恶变的患者缺乏有效的早期甄别手段。前期研究发现头颈鳞癌中IL-1a3’UTR区rs3783553基因多态性具有功能性，可增加IL-1a血清学水平及HPV阳性患者的肿瘤易感性，但IL-1a与HPV病毒的交互作用机制尚有待探索。故拟通过构建不同基因型及HPV感染状态的细胞系，验证rs3783553基因多态性对IL-1a体外表达的调控，阐明HPV感染对IL-1a下游NFkB等信号通路的影响，以及IL-1a对E6、E7蛋白表达的调控，对比发生癌变与未癌变的成人上呼吸道乳头状瘤中IL-1a3’UTR区rs3783553基因多态性，以及IL-1a血清水平与预后的关系，以明确IL-1a与HPV在疾病进展中的交互协同作用。为该病的个体化精准医疗提供新的临床思路和方法。

随着HPV感染率增加，成人上呼吸道乳头状瘤的发病率逐年递增，且部分患者易恶变。目前对易恶变的患者缺乏有效的早期甄别手段。IL-1a3’UTR区rs3783553基因多态性具有功能性，可增加IL-1a血清学水平及HPV阳性患者的肿瘤易感性，研究进一步通过构建不同基因型及HPV感染状态的细胞系，验证rs3783553基因多态性对IL-1a体外表达的调控，以及IL-1a对E6、E7蛋白表达的调控，对比发生癌变与未癌变的成人上呼吸道乳头状瘤中IL-1a3’UTR区rs3783553基因多态性，证实IL-1a血清水平与预后的关系，IL-1a与HPV在疾病进展存在交互协同作用。HPV16阳性乳头状瘤中，IL-1α、IL-1R、IL-1β、AIM2 和Caspase-1表达均增高;且IL-1β表达升高组较IL-1β降低组的复发及恶变风险升高。HPV是否通过AIM2/Caspase通路调控，以及相关炎症免疫因子改变仍将继续深入研究。