MTAP在前列腺癌中的表达及对免疫细胞的影响初探

The expression of MTAP in prostate cancer and its effect on immune cells

摘要:

目的 探究甲硫腺苷磷酸化酶（methylthioadenosine phosphorylase，MTAP）在前列腺癌不同临床阶段的表达差异及其对免疫细胞的影响。方法 从TCGA和GTEx数据库中获取MTAP的表达谱数据，利用生物信息学方法进行泛癌分析。免疫组化验证上述结论并探究MTAP与临床病理指标之间的关联。RT-qPCR和Western blot检测MTAP在不同前列腺癌细胞系中的表达水平，分析MTAP与肿瘤恶性程度之间的关联。生物信息学方法分析前列腺癌中MTAP与免疫细胞的关联并进行免疫组化验证。结果 在前列腺癌中，MTAP的表达在肿瘤发生早期升高后逐渐降低，与T分期和Gleason评分呈负相关（r_s=-0.576，P=0.000，r_s=-0.284，P=0.020）。MTAP与多种免疫细胞存在相关关系，其中MTAP与CD4⁺T细胞呈正相关（r=0.643，P=0.000），与NK CD56^bright细胞呈负相关（r=-0.570，P=0.000）。结论 前列腺癌中，MTAP的表达呈现早期升高后逐渐下降的趋势，与T分期和Gleason评分呈负相关。MTAP对免疫细胞的浸润和细胞功能的发挥有调节作用，是一种潜在的生物学标志物和免疫治疗靶点。

Abstract:

Objective To explore the expression of Methylthioadenosine phosphorylase（MTAP） in different clinical stages of prostate cancer and its correlation with immune cells.Methods The expression profile of MTAP was obtained from TCGA and GTEx databases，and pancarcinoma was analyzed by bioinformatics method. Immunohistochemistry verified the conclusions above and explored the correlation between MTAP and clinicopathological features. The expression levels of MTAP in different prostate cancer cell lines were detected by RT-qPCR and Western blot，and the correlation between MTAP and the degree of malignancy was analyzed. The correlatoin between MTAP and immune cells in prostate cancer was analyzed by bioinformatics and verified by immunohistochemistry.Results In prostate cancer，the expression of MTAP increased at early stage and then decreased gradually，and was negatively correlated with T stage and Gleason score（r_s=-0.576，P=0.000，r_s=-0.284，P=0.020）. MTAP was correlated with a variety of immune cells，among which MTAP was positively correlated with CD4⁺T cells（r=0.643，P=0.000），was significantly negatively correlated with NK CD56^bright cells（r=-0.570，P=0.000）.Conclusion In prostate cancer，the expression of MTAP increased at the early stage and then decreased gradually，which was negatively correlated with T stage and Gleason score. MTAP can regulate the infiltration and function of immune cells，and is a potential biomarker and immunotherapy target.