Validation of Gene Profiles for Analysis of Regional Lymphatic Metastases in Head and Neck Squamous Cell Carcinoma
Validation of Gene Profiles for Analysis of Regional Lymphatic Metastases in Head and Neck Squamous Cell Carcinoma
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DOI：
10.3389/fmolb.2020.00003
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发表时间：
2020-02-04
影响因子：
5
通讯作者：
Hu, Jingzhou
中科院分区：
文献类型：
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作者：
Hu, Zhenrong;Yang, Ranran;Hu, Jingzhou
头颈部鳞状细胞癌（HNSCC）的进展依赖于癌症干细胞（CSC）和免疫抑制。本研究旨在评估HNSCC原发肿瘤和淋巴结中CSC的分布和特征性免疫抑制状态。共303个淋巴结从25例患者，以及肿瘤和邻近的正常组织样本，通过定量PCR检测CSC的标志物和特征性的免疫抑制进行了评估。还分析了癌症基因组图谱（TOGA）数据集中所选基因的表达。与癌旁正常组织相比，肿瘤组织中肿瘤干细胞标志物（ALDH1L1、PECAM 1、PROM 1）表达下调，而免疫抑制标志物FOXP3、CD47、EGFR、SOX 2、TGF β 1表达上调。在淋巴结中，与原发肿瘤相比，CSC和免疫抑制标记物的表达显著上调。选定的CSC和免疫抑制标志物的mRNA表达在转移水平II中表现出最高表达，然后在转移水平III中下降，并在转移水平IV和V中保持恒定，并降低值。这些结果揭示了与HNSCC转移位点相关的独特遗传学特征和淋巴道转移的潜在途径，这有助于解释为什么II级淋巴结转移的发生率较高，以及为什么临床上很少发现直接跳跃转移到IV级或V级。
The progress of Head and Neck Squamous Cell Carcinoma (HNSCC) is dependent on both cancer stem cells (CSCs) and immune suppression. This study was designed to evaluate the distribution of CSCs and the characteristic immune suppression status in HNSCC primary tumors and lymph nodes. A total of 303 lymph nodes from 25 patients, as well as tumor and adjacent normal tissue samples, were evaluated by a quantitative PCR assay of the markers of CSCs and the characteristic immune suppression. Expressions of selected genes in The Cancer Genome Atlas (TOGA) datasets were also analyzed. In the primary tumors, we found that expressions of CSCs markers (ALDH1L1, PECAM1, PROM1) were down-regulated, while immune suppression markers FOXP3, CD47, EGFR, SOX2, and TGFB1 were up-regulated significantly when compared to that in adjacent normal tissues. In the lymph nodes, expressions of both CSCs, and immune suppression markers were upregulated significantly compared with that in primary tumors. The mRNA expression of selected CSCs and immune suppression markers exhibited the highest expression in the level II of metastasis, then declined in the level III and remained constant at a reduced value in levels IV and V of metastases. These results reveal a comprehensive understanding of the unique genetic characteristics associated with metastatic loci and potential routes of lymphatic dissemination of HNSCC, which helps to explain why the level II has a high incidence of lymph node metastasis, and why skip metastasis straight to the level IV or level V is rarely found in the clinic.