Wnt/β-catenin信号通路对日光性角化病相关基因蛋白表达的影响

Effect of Wnt/beta-catenin signaling pathway on the expression of genes related to the pathogenesis of solar keratosis

目的 观察日光性角化病(AK)患者中Wnt/β-catenin信号通路的相关基因蛋白的表达情况,分析其在AK发病机制的作用。方法 回顾性分析资阳市第一人民医院2010年3月至2017年5月收治的45例AK确诊患者(AK组)、45例鳞癌患者(鳞癌组)以及50例健康人(正常组)的临床资料。然后对患者的石蜡组织标本进行组织学病理检查,分析AK组患者的病理学特点;通过免疫组织化学法检测组织细胞中的β-catenin以及降解基底膜的基质金属蛋白酶(MMP-2)的表达情况;运用RT-PCR的方法,检测与凋亡相关的Fas、Fas L以及细胞周期调节蛋白P-53相关基因的表达情况。结果 组织病理结果显示,AK患者组织真皮的浅层发生有嗜碱性病变,组织表皮的下层细胞排列紊乱。免疫组化结果显示,AK组、鳞癌组以及正常组MMP-2阳性分别为41例、35例、8例,β-catenin阳性分别为27例、12例、1例,Livin阳性分别为28例、15例、3例,Caspase-3阳性分别为25例、16例、2例;MMP-2、Livin、Caspase-3和β-catenin阳性率情况:AK组>鳞癌组>正常组,差异具有统计学意义(P <0. 05)。PCR结果显示,鳞癌组患者的Fas、Fas L以及P-53表达水平分别是AK组患者的0. 24、2. 92以及3. 47倍,且两组患者目的基因的△CT差异显著,具有统计学意义(P <0. 05)。结论 Wnt/β-catenin信号通路影响细胞中基质金属蛋白酶MMP-2、细胞凋亡相关基因(Fas、Fas L)和P53的表达,在AK的发病机制中起着重要的作用。

Objective To observe the expression of Wnt/β-catenin signaling pathway related genes in patients with solar keratosis(AK),and to analyze the role of Wnt/β-catenin signaling in the pathogenesis of AK,providing a reference for the clinical diagnosis and treatment of AK.Methods The clinical data of 45 patients with AK diagnosed(AK group),45 patients with squamous cell carcinoma(SCC)and 50 normal patients(normal group)were retrospectively analyzed in our hospital from March 2010 to May 2017.The histopathological examination was performed to analyze the pathological features of AK group.The expression ofβ-catenin and matrix metalloproteinase(MMP-2)in the basement membrane was detected by immunohistochemistry.Real-time RT-PCR was used to detect the expression of apoptosis-related Fas,FasL and cell cycle regulatory protein P-53 related genes.Results The histopathological results showed that basophilic lesions occurred in the superficial layers of the dermis and the underlying cells of the epidermis were disordered.Immunohistochemical results showed that positive mmp-2 of the AK group,squamous cell carcinoma group and normal group were 41,35 and 8,positive of human and human squamous cell carcinoma group were 27,12 and 1,positive of Livin were 28,15,3 and caspase-3 were 25,16 and 2,respectively.PCR results showed that the expression levels of Fas,FasL and p-53 in squamous cell carcinoma group were 0.24,2.92,and 3.47 times of those in AK group,respectively.In addition,there were significant differences in the bearing CT of the target gene between the two groups,showing statistical significance(P<0.05).Conclusion The Wnt/β-catenin signaling pathway plays an important role in the pathogenesis of AK disease by affecting the expression of matrix metalloproteinase-2,apoptosis-related genes(Fas,FasL)and P53.