基于TCGA数据库探讨宫颈癌免疫细胞浸润模式与临床特征和预后的相关性

Study on the relationship between immune cell infiltration pattern and clinical characteristics and prognosis of cervical cancer based on TCGA database

目的:探讨宫颈癌免疫细胞浸润模式与临床特征和预后的相关性。方法:从公共数据库癌症基因组图谱(TCGA)中下载所有宫颈癌转录本数据及相关临床数据,通过Cibersort软件计算22种浸润性免疫细胞类型的相对比例。采用Perl评估宫颈癌免疫细胞浸润模式与临床特征(年龄、临床分期、肿瘤分级)的相关性,通过K-M Log-Rank法计算宫颈癌免疫细胞浸润模式与生存的相关性。结果:采用Cibersort评估了306例宫颈癌和3例正常组织免疫细胞的分布情况。宫颈癌肿瘤组织与正常组织相比,静息状态树突细胞、活化的树突细胞、M1巨噬细胞及活化的CD4^(+)记忆性T细胞含量较高;M2巨噬细胞、中性粒细胞、调节性T细胞及活化的肥大细胞含量较低。M1巨噬细胞、未活化的CD4^(+)记忆性T细胞、γδT细胞的含量与患者年龄呈正相关(P<0.05);滤泡辅助性T细胞、活化和未活化的自然杀伤(NK)细胞和幼稚CD4^(+)T细胞的含量与患者年龄呈负相关(P<0.05);静息状态树突状细胞构成比高者总生存期短,而滤泡辅助性T细胞构成比高者总生存期长(P<0.05)。结论:与正常组织相比,宫颈癌组织中免疫细胞的组成存在一定的特异性,可为该病的早期筛查与诊断提供参考;不同年龄段患者可能存在不同的免疫细胞浸润模式,临床可以此为基础,探索药物靶标;静息状态树突状细胞和滤泡辅助性T细胞或可作为宫颈癌临床免疫治疗的疗效预测指标。

Objective:To investigate the relationship between the infiltration pattern of immune cells and the clinical characteristics and prognosis of cervical cancer.Methods:All transcripts and clinical data of cervical cancer were downloaded from TCGA,and the relative proportion of 22 invasive immune cell types was calculated by Cibersort software.Perl was used to evaluate the correlation between the infiltration pattern of cervical cancer immune cells and clinical characteristics(age,clinical stage,tumor grade).K-M Log-Rank method was used to calculate the correlation between the infiltration pattern of cervical cancer immune cells and survival.Results:The distribution of immune cells in 306 cases of cervical cancer and 3 cases of normal tissues was evaluated by Cibersort.Compared with normal cervical cancer tissues,the contents of resting dendritic cells,activated dendritic cells,M1 macrophages and activated CD4^(+)memory T cells were higher,while contents of M2 macrophages,neutrophils,regulatory T cells and activated mast cells were lower.The contents of M1 macrophages,activated CD4^(+)memory T cells andγδT cells were positively correlated with the age of patients(P<0.05);the contents of follicular helper T cells,activated and inactive natural killer(NK)cells,and immature CD4 T cells were negatively correlated with the age of patients(P<0.05);the total survival time of the patients with higher composition of resting state dendritic cells was shorter,while that of the pactients with higher composition of follicular helper T cells was longer(P<0.05).Conclusion:Compared with normal tissue,the composition of immune cells in cervical cancer tissue has certain specificity,which can provide reference for early screening and diagnosis of the disease;patients of different ages may have different immune cell infiltration patterns,which can be used as the basis for clinical exploration of drug targets;resting state dendritic cells and follicular helper T cells in cervical cancer can be used as the possible outcome predictors in immunotherapy of clinical cervical cancer.