期刊
FRONTIERS IN ENDOCRINOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2020.570604
关键词
papillary thyroid carcinoma; immune cell infiltration; tumor microenvironment; immune escape; TCGA; CIBERSORT
资金
- National Natural Science Foundation of China [81600602]
Background Papillary thyroid cancer has been associated with chronic inflammation. A systematic understanding of immune cell infiltration in PTC is essential for subsequent immune research and new diagnostic and therapeutic strategies. Methods Three different algorithms, single-sample gene set enrichment analysis (ssGSEA), immune cell marker and CIBERSORT, were used to evaluate immune cell infiltration levels (abundance and proportion) in 10 data sets (The Cancer Genome Atlas [TCGA], GSE3467, GSE3678, GSE5364, GSE27155, GSE33630, GSE50901, GSE53157, GSE58545, and GSE60542; a total of 799 PTC and 194 normal thyroid samples). Consensus unsupervised clustering divided PTC patients into low-immunity and high-immunity groups. Weighted gene coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA) were used to analyze the potential mechanisms causing differences in the immune response. Results Compared with normal tissues, PTC tissues had a higher overall immune level and higher abundance levels and proportions of M2 macrophages, Tregs, monocytes, neutrophils, dendritic cells (DCs), mast cells (MCs), and M0 macrophages. Compared with early PTC, advanced PTC showed higher immune infiltration and higher abundance levels and proportions of M2 macrophages, Tregs, monocytes, neutrophils, DCs, MCs, and M0 macrophages. Compared to the low-immunity group, the high-immunity group exhibited more advanced stages, larger tumor sizes, greater lymph node metastases, higher tall-cell PTCs, lower follicular PTC proportions, more BRAF mutations, and fewer RAS mutations. Epstein-Barr virus (EBV) infection was the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for key module genes. Conclusions In human PTC, M2 macrophages, Tregs, monocytes, neutrophils, DCs, MCs, and M0 macrophages appear to play a tumor-promoting role, while M1 macrophages, CD8+ T cells, B cells, NK cells, and T follicular helper (T-FH) cells (including eosinophils, gamma delta T cells, and Th17 cells with weak supporting evidence) appear to play an antitumor role. During the occurrence and development of PTC, the overall immune level was increased, and the abundance and proportion of tumor-promoting immune cells were significantly increased, indicating that immune escape had been aggravated. Finally, we speculate that EBV may play an important role in changing the immune microenvironment of PTC tumors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据