皮肤黑色素瘤免疫细胞浸润模式及其与预后的相关性分析

Infiltration patterns of immune cells in cutaneous melanoma and its correlation with prognosis

摘要:

目的： 研究皮肤黑色素瘤的免疫细胞浸润模式，以及免疫细胞浸润与患者预后的关系。方法： 从癌症基因组图谱（the cancer genome atlas，TCGA）数据库下载皮肤黑色素瘤转录本数据及相关临床数据，使用Cibersort软件的反卷积法计算22种免疫细胞的占比，采用R编程语言计算免疫细胞占比与性别的相关性，采用K-M生存分析log-rank法计算每种免疫细胞占比与总生存期（overall survival，OS）的相关性。结果： 从TCGA数据库中得到472例基因转录本数据，包含黑色素瘤组织470例，正常皮肤组织2例。每个样本检测基因位点60 483个，提取mRNA 19 658个。数据校正后使用Cibersort软件的反卷积法得到22种免疫细胞的占比数据，采用P<0.05筛选样本，得到黑色素瘤组织219例，正常组织1例。M0巨噬细胞、CD8⁺T细胞、M2巨噬细胞在黑色素瘤中浸润水平较高；CD8⁺T细胞与M0巨噬细胞（-0.62）、未活化的记忆性CD4⁺T细胞与CD8⁺T细胞（-0.53）的占比相关性较强；K-M生存分析显示未活化的肥大细胞（P=0.015）、未活化的NK细胞（P=0.025）组成比例高者患者预后差，γδT细胞（P=0.043）组成比例高者预后更好。女性黑色素瘤患者中未活化的肥大细胞占比较男性黑色素瘤患者少（P=0.028）。结论： 皮肤黑色素瘤中浸润的免疫细胞组成存在差异，浸润的免疫细胞可能是决定预后的重要因素。这有助于开发有效的免疫疗法。

Abstract:

Objective: To study the infiltration patterns of immune cells in cutaneous melanoma and to explore the relationship between immune cells infiltration and clinical prognosis. Methods: Transcripts and related clinical data of cutaneous melanoma were downloaded from the cancer genome atlas (TCGA) database. The proportion of 22 kinds of immune cells were calculated by deconvolution method with Cibersort software. The correlation between immune cells proportion and gender was calculated by R programming language, and K-M survival analysis with log-rank method was used to determine the correlation between each kind of immune cells and overall survival (OS). Results: A total of 472 gene transcripts were obtained from the TCGA database, including 470 cases of cutaneous melanoma and 2 cases of normal tissues. Each sample detected 60, 483 genetic loci and extracted 19, 658 mRNAs. After data correction, the proportion of 22 kinds of immune cells was obtained by deconvolution method with Cibersort software. Totally 219 cases of cutaneous melanoma and 1 case of normal skin tissue were obtained by screening samples with the criteria P<0.05. M0 macrophages, CD8⁺T cells, and M2 macrophages were the types of immune cells with higher levels of infiltration in melanoma tissues. The strongly correlated immune cells included CD8⁺T cells and M0 macrophages (-0.62), and inactivated CD4⁺T cells and CD8⁺T cells (-0.53).K-M survival analysis showed that patients with the higher proportion of inactivated mast cells (P=0.015) and inactivated NK cells (P=0.025) had worse prognosis, and patients with the higher proportion of γδT cells (P=0.043) had better prognosis. The proportion of inactive mast cells in female with melanoma was less than that in male (P=0.028). Conclusion: There are differences in the composition of infiltrated immune cells in cutaneous melanoma. These cells are likely to be important determinants of prognosis, which helps us develop effective immunotherapy.