The neuropeptide calcitonin gene-related peptide links perineural invasion with lymph node metastasis in oral squamous cell carcinoma.
The neuropeptide calcitonin gene-related peptide links perineural invasion with lymph node metastasis in oral squamous cell carcinoma.
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神经肽降钙素基因相关肽将口腔鳞状细胞癌的神经周围浸润与淋巴结转移联系起来。
DOI：
10.1186/s12885-021-08998-9
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发表时间：
2021-11-20
期刊：
影响因子：
3.8
通讯作者：
Ji T
中科院分区：
文献类型：
--
作者：
Zhang Y;Chen M;Liu Z;Wang X;Ji T
尽管众所周知神经周围浸润（perineural invasion，PNI）与口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）的淋巴结转移（lymph node metastasis，LNM）相关并能预测LNM，但PNI与LNM之间的临床和分子相关性尚未阐明，迫切需要术前生物标志物预测OSCC的LNM。PNI和LNM之间的相关性进行了回顾性评估，使用一个队列的218例诊断为口腔鳞癌。基于TCGA数据库筛选候选神经肽，并通过免疫组织化学和Western印迹分析进行验证。采用酶联免疫吸附法（ELISA）检测患者血浆中降钙素基因相关肽（CGRP）。体外实验观察CGRP对口腔鳞癌细胞的作用。伴PNI的口腔鳞癌患者淋巴结转移发生率明显高于伴PNI的口腔鳞癌患者（69.86% vs.26.2%，P < 0.0001，n = 218）。CGRP表达上调PNI龛和转移淋巴结，并与口腔鳞癌患者的总体生存率差。OSCC患者（n = 70）术前血浆CGRP水平高于健康志愿者（n = 60）（48.59 vs.14.58pg/ml，P < 0.0001），并与LNM（P < 0.0001）和PNI（P = 0.0002）相关。术前血浆CGRP水平单独预测LNM的AUC值为0.8088，CGRP水平结合术前T分期达到AUC值0.8590。CGRP促进OSCC细胞的增殖和迁移能力，这可以通过药物或基因阻断CGRP受体来拮抗。神经肽CGRP在口腔鳞癌的PNI和LNM之间起着重要的联系，术前血浆CGRP水平可用于预测口腔鳞癌的LNM。在线版本包含补充材料，可通过10.1186/s12885-021-08998-9获得。
Although perineural invasion (PNI) is well-known to be correlated with and able to predict lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC), the clinical and molecular correlation between PNI and LNM has not been elucidated, and preoperative biomarkers for LNM prediction in OSCC are urgently needed. The correlation between PNI and LNM was retrospectively evaluated using a cohort of 218 patients diagnosed with OSCC. Candidate neuropeptides were screened based on TCGA database and verified via immunohistochemistry and Western blot analyses. ELISA was used to detect calcitonin gene-related peptide (CGRP) in patient plasma. In vitro assays were used to explore the effects of CGRP on OSCC cells. OSCC patients with PNI had a higher incidence of LNM (69.86% vs. 26.2%, P < 0.0001, n = 218). CGRP expression was upregulated in the PNI niche and in metastatic lymph nodes, and was correlated with poor overall survival of OSCC patients. Preoperative plasma CGRP levels were higher in OSCC patients (n = 70) compared to healthy donors (n = 60) (48.59 vs. 14.58 pg/ml, P < 0.0001), and were correlated with LNM (P < 0.0001) and PNI (P = 0.0002). Preoperative plasma CGRP levels alone yielded an AUC value of 0.8088 to predict LNM, and CGRP levels combined with preoperative T stage reached an AUC value of 0.8590. CGRP promoted proliferation and migration abilities of OSCC cells, which could be antagonized by either pharmacological or genetic blockade of the CGRP receptor. The neuropeptide CGRP links PNI and LNM in OSCC, and preoperative plasma CGRP levels can be used to predict LNM in OSCC. The online version contains supplementary material available at 10.1186/s12885-021-08998-9.
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影响因子：
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作者：
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通讯作者：
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