Siglec-15 Is an Immune Suppressor and Potential Target for Immunotherapy in the Pre-Metastatic Lymph Node of Colorectal Cancer

作者：Hang Du, Jingling Tang, Xiaoyun Li, Xinjun Wang, Liyun Wu, Ruyi Zhang, Pingsheng Hu, Yuan Yang · 发表于：Frontiers in Cell and Developmental Biology · 年份：2021 · DOI：10.3389/fcell.2021.691937 · 被引用次数：20 · 研究领域：Genetic factors in colorectal cancer、Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis

Lymph node metastasis indicates a poor prognosis in colorectal cancer. To better understand the underlying mechanisms of lymph node metastasis, we analyzed transcriptome characteristics of the pre-metastatic lymph node, a putative microenvironment favorable for the seeding and proliferation of cancer cells. Thus, we tried to compare and elucidate the transcriptional and immune characteristics of sentinel lymph nodes (SNs) with matched non-sentinel lymph nodes (NSNs) in colorectal cancer patients. In this study, a total of 38 pairs of SNs and NSNs were collected, in which 26 pairs of non-metastatic lymph nodes were subjected to RNA-seq and bioinformatics analysis for the gene expression profiles. There were 16 differentially expressed genes between SNs and NSNs being identified, including 9 upregulated and 7 downregulated genes in SN. Gene Ontology (GO) classification analysis revealed that the differentially expressed genes were mainly involved in leukocyte differentiation, chemokine secretion, and immune system regulation. In the meantime, gene set enrichment analysis (GSEA) showed that immune-related signaling pathways, such as transforming growth factor beta (TGF-β) signaling and tumor necrosis factor alpha (TNF-α)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, were enriched in NSN, while cell proliferation–related signaling pathways were enriched in SN, including MYC signaling and G2M checkpoint signaling. We further identified SIGLEC15 ...