骨肉瘤肿瘤微环境中免疫细胞浸润和免疫相关基因的特征。

Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of osteosarcoma cancer.

机构信息

Department of Spine Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China.

Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China.

出版信息

BMC Cancer. 2021 Dec 18;21(1):1345. doi: 10.1186/s12885-021-09042-6.

DOI:10.1186/s12885-021-09042-6

PMID:34922489

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8684084/

Abstract

BACKGROUNDS

Osteosarcomas are one of the most common primary malignant tumors of bone. It primarily occurs in children and adolescents, with the second highest incidence among people over 50 years old. Although there were immense improvements in the survival of patients with osteosarcoma in the past 30 years, targetable mutations and agents of osteosarcomas still have been generally not satisfactory. Therefore, it is of great importance to further explore the highly specialized immune environment of bone, genes related to macrophage infiltration and potential therapeutic biomarkers and targets.

METHODS

The 11 expression data sets of OS tissues and the 11 data sets of adjacent non-tumorous tissues available in the GEO database GSE126209 were used to conduct immune infiltration analysis. Then, through WGCNA analysis, we acquired the co-expression modules related to Mast cells activated and performed the GO and KEGG enrichment analysis. Next, we did the survival prognosis analysis and plotted a survival curve. Finally, we analyzed the COX multivariate regression of gene expression on clinical parameters and drew forest maps for visualization by the forest plot package.

RESULTS

OS disease-related immune cell populations, mainly Mast cells activated, have higher cell content (p = 0.006) than the normal group. Then, we identified co-expression modules related to Mast cells activated. In sum, a total of 822 genes from the top three strongest positive correlation module MEbrown4, MEdarkslateblue and MEnavajowhite2 and the strongest negative correlation module MEdarkturquoise. From that, we identified nine genes with different levels in immune cell infiltration related to osteosarcoma, eight of which including SORBS2, BAIAP2L2, ATAD2, CYGB, PAMR1, PSIP1, SNAPC3 and ZDHHC21 in their low abundance have higher disease-free survival probability than the group in their high abundances.

CONCLUSION

These results could assist clinicians to select targets for immunotherapies and individualize treatment strategies for patients with OS.

摘要

背景

骨肉瘤是最常见的原发性骨恶性肿瘤之一。它主要发生在儿童和青少年中，其次是 50 岁以上人群。尽管过去 30 年骨肉瘤患者的生存率有了很大提高，但骨肉瘤的靶向突变和药物仍然普遍不尽如人意。因此，进一步探索骨的高度特化免疫环境、与巨噬细胞浸润相关的基因以及潜在的治疗生物标志物和靶点非常重要。

方法

使用 GEO 数据库 GSE126209 中可用的 11 个骨肉瘤组织表达数据集和 11 个相邻非肿瘤组织数据集进行免疫浸润分析。然后，通过 WGCNA 分析，我们获得了与 Mast cells activated 相关的共表达模块，并进行了 GO 和 KEGG 富集分析。接下来，我们进行了生存预后分析并绘制了生存曲线。最后，我们分析了基因表达对临床参数的 COX 多变量回归，并通过 forestplot 包绘制了森林图进行可视化。

结果

骨肉瘤疾病相关免疫细胞群，主要是 Mast cells activated，细胞含量更高（p=0.006）。然后，我们确定了与 Mast cells activated 相关的共表达模块。共有 822 个基因来自三个最强正相关模块 MEbrown4、MEdarkslateblue 和 MEnavajowhite2 和最强负相关模块 MEdarkturquoise。从中，我们确定了 9 个与骨肉瘤免疫细胞浸润相关的基因，其中 8 个基因，包括 SORBS2、BAIAP2L2、ATAD2、CYGB、PAMR1、PSIP1、SNAPC3 和 ZDHHC21，其低丰度的免疫细胞浸润相关基因具有更高的无病生存率，而高丰度的基因则相反。