通过生物信息学方法评估Treg细胞在泌尿系肿瘤中的浸润模式

Bioinformatic evaluation of the infiltration pattern of Treg cells in urinary tumors

目的研究调节性T细胞(Treg)在肾透明细胞癌、膀胱癌、前列腺癌组织中的分布及对预后的影响。方法从TCGA数据库下载肾透明细胞癌、膀胱癌、前列腺癌的转录数据及临床资料,通过CIBERSORT软件包预测肿瘤组织中22种免疫细胞的浸润模式,应用R语言分析Treg细胞与其他免疫细胞及与预后的相关性。并利用ssGSEA富集分析Treg细胞与IFN-γ相关通路的相关性。结果Treg在肾透明细胞癌及前列腺癌组织中的浸润水平较正常组织高,而在膀胱癌中无显著差异。3种肿瘤中Treg细胞与其他免疫细胞表现为弱相关。Treg与肿瘤预后相关性分析显示Treg在肾透明细胞癌中高密度浸润与低生存率显著相关(P=0.01),而在膀胱癌中高密度浸润与高生存率相关(P=0.045),Treg的浸润程度与前列腺癌患者的生存率无明显相关性。肾透明细胞癌中Treg与不同T分期相关(P=0.002)。Treg与IFN-γ相关通路在肾透明细胞癌表现为弱的正相关,在膀胱癌、前列腺癌中则为较弱的负相关(|r|<0.2,P<0.05)。结论Treg细胞在肾透明细胞癌和膀胱癌中高浸润水平对应的预后不一致,这可能与肿瘤所处炎性环境相关,未来可根据Treg细胞在特定肿瘤中的浸润模式针对Treg开发免疫治疗的新策略。

Objective To investigate the distribution of regulatory T cells(Treg)in renal clear cell carcinoma,bladder cancer and prostate cancer,and to explore the effects on the prognosis.Methods The transcriptional and clinical data of renal clear cell carcinoma,bladder cancer and prostate cancer were downloaded from the TCGA database.The infiltration patterns of 22 kinds of immune cells in tumor tissues were predicted with CIBERSORT software package.The correlation between Treg cells and other immune cells as well as the prognosis was analyzed with R software.The correlation between Treg cells and IFN-γrelated pathway was analyzed with ssGSEA enrichment.Results Treg cells showed a higher infiltration density in renal clear cell carcinoma and prostate carcinoma than in normal tissues,while there was no significant difference in bladder cancer.Treg cells were weakly correlated with other immune cells in the 3 types of tumors.High-density infiltration of Treg cells was significantly correlated with low survival rate in renal clear cell carcinoma(P=0.01),but with high survival rate in bladder cancer(P=0.045),while the infiltration degree of Treg cells was not significantly correlated with survival rate of prostate cancer patients.Treg cells were correlated with different T stages in renal clear cell carcinoma(P=0.002).There was a weak correlation between Treg cells and IFN-γrelated pathway in the 3 types of tumors(|r|<0.2,P<0.05).Conclusion The high infiltration level of Treg cells predicts different prognosis of renal clear cell carcinoma and bladder cancer,which may be related to the expression of the IFN-γpathway.In the future,new immunotherapy strategies can be developed according to the infiltration pattern of Treg cells in specific tumors.