Differential gene expression of tumor-infiltrating CD33(+) myeloid cells in advanced- versus early-stage colorectal cancer.

Differential gene expression of tumor-infiltrating CD33(+) myeloid cells in advanced- versus early-stage colorectal cancer.
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晚期与早期结直肠癌中肿瘤浸润性CD33(+)髓样细胞的差异基因表达

DOI:
10.1007/s00262-020-02727-0
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发表时间:
2021-03
期刊:
Cancer immunology, immunotherapy : CII
影响因子:
--
通讯作者:
Elkord E
Elkord E
中科院分区:
其他
文献类型:
--
作者:
Toor SM;Taha RZ;Sasidharan Nair V;Saleh R;Murshed K;Abu Nada M;Elkord E

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结直肠癌(CRC)具有很高的死亡率,特别是在疾病晚期的患者中,他们通常对治疗没有反应。肿瘤微环境的细胞成分基本上决定了疾病的进展和对治疗的反应。不同骨髓细胞亚群在结直肠癌肿瘤中的扩增已有报道。然而,肿瘤浸润性骨髓细胞在疾病进展中具有促肿瘤和抗肿瘤的作用。在这项研究中,我们对不同疾病阶段的大块结直肠癌肿瘤的髓系细胞(CD33+)进行了转录组学分析。我们确定了晚期和早期结直肠癌患者之间差异表达的基因和途径。我们发现,在晚期患者的CD33+骨髓细胞中,促血管生成和缺氧相关基因上调,而与免疫和炎症反应相关的基因下调,这意味着免疫细胞的募集和激活可能在晚期疾病中受到损害。此外,我们利用来自癌症基因组图谱的数据,通过比对肿瘤浸润性骨髓细胞中顶部上调和下调的基因,确定了一个独特的“预后不良CD33+基因特征”。我们的研究结果表明,该基因标记是CRC患者疾病特异性生存的独立预后指标,可能反映了其临床重要性。本文的在线版本(10.1007/s00262-020-02727-0)包含补充资料,仅供授权用户使用。
Colorectal cancer (CRC) has high mortality rates, especially in patients with advanced disease stages, who often do not respond to therapy. The cellular components of the tumor microenvironment are essentially responsible for dictating disease progression and response to therapy. Expansion of different myeloid cell subsets in CRC tumors has been reported previously. However, tumor-infiltrating myeloid cells have both pro- and anti-tumor roles in disease progression. In this study, we performed transcriptomic profiling of cells of myeloid lineage (CD33+) from bulk CRC tumors at varying disease stages. We identified differentially expressed genes and pathways between CRC patients with advanced stage and early stages. We found that pro-angiogenic and hypoxia-related genes were upregulated, while genes related to immune and inflammatory responses were downregulated in CD33+ myeloid cells from patients with advanced stages, implying that immune cell recruitment and activation could be compromised in advanced disease stages. Moreover, we identified a unique “poor prognosis CD33+ gene signature” by aligning top upregulated and downregulated genes in tumor-infiltrating myeloid cells from our analyses with data from The Cancer Genome Atlas. Our results showed that this gene signature is an independent prognostic indicator for disease-specific survival in CRC patients, potentially reflecting its clinical importance. The online version of this article (10.1007/s00262-020-02727-0) contains supplementary material, which is available to authorized users.
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