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非小细胞肺癌微转移前哨淋巴结中上皮-间充质转化相关标志物表达的临床意义。

Clinical significance of epithelial-mesenchymal transition-related markers expression in the micrometastatic sentinel lymph node of NSCLC.

机构信息

Department of Molecular Biology, Hospital Universitario de la Ribera, Ctra. Corbera, km. 1, 46600, Alzira, Spain.

Department of Thoracic Surgery, Hospital Universitario de la Ribera, Alcira, Spain.

出版信息

Clin Transl Oncol. 2020 Mar;22(3):381-391. doi: 10.1007/s12094-019-02138-3. Epub 2019 May 28.

Abstract

OBJECTIVES

Metastatic lymph node affectation is the main prognostic factor in localised lung cancer. However, the pathological study of lymph nodes reveals tumour relapse for 20% of patients after oncological curative surgery. Recently, EMT (epithelial-mesenchymal transition) has been established as one of the main factors related to lymphatic dissemination and metastasis. This study evaluated the prognostic value of EMT-related gene expression in micrometastatic sentinel lymph nodes (SLN) of non-small cell lung cancer (NSCLC) patients.

METHODS

The presence of genes CDH1, CDH2, VIM, TWIST1, SNAI1, SNAI2, ZEB1, and ZEB2 in mRNA was analysed in tumours and in the SLN of NSCLC patients for whom surgery was planned for treatment. The significant association between the expression level of EMT-related markers and patients' clinicopathological characteristics and relapse was assessed.

RESULTS

Of the 96 patients, 56 (58.33%) presented molecular micrometastasis in SLN, which showed higher CDH1, CDH2, and VIM expressions than non-micrometastatic ones. An association linking a low CDH1/CDH2 ratio in SLN with molecular micrometastasis, adenocarcinoma, and non-smoking patients was found. The multivariate Cox regression analysis proved the prognostic accuracy of the CDH1/CDH2 ratio in SLN.

CONCLUSIONS

The molecular EMT status of SLN could be used as an independent prognosis predictor in early stage NSLCL patients, and as a new tool to better stratify and predict patient outcomes.

摘要

目的

淋巴结转移是局部肺癌的主要预后因素。然而,淋巴结的病理研究显示,20%的肿瘤患者在接受肿瘤治愈性手术后会出现肿瘤复发。最近,上皮-间充质转化(EMT)被确定为与淋巴扩散和转移相关的主要因素之一。本研究评估了 EMT 相关基因表达在非小细胞肺癌(NSCLC)患者微转移前哨淋巴结(SLN)中的预后价值。

方法

分析计划手术治疗的 NSCLC 患者肿瘤和 SLN 中 CDH1、CDH2、VIM、TWIST1、SNAI1、SNAI2、ZEB1 和 ZEB2 基因的 mRNA 表达。评估 EMT 相关标志物表达水平与患者临床病理特征和复发的显著相关性。

结果

96 例患者中,56 例(58.33%)SLN 存在分子微转移,其 CDH1、CDH2 和 VIM 的表达高于非微转移者。在 SLN 中,CDH1/CDH2 比值低与分子微转移、腺癌和非吸烟者有关。多变量 Cox 回归分析证明了 SLN 中 CDH1/CDH2 比值的预后准确性。

结论

SLN 的分子 EMT 状态可作为早期 NSCLC 患者独立的预后预测指标,并作为一种新的工具,更好地分层和预测患者的结局。

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