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

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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.

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Funding

This study was funded by a grant by Fundación para el fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (UGP-15-137).

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Authors and Affiliations

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

    A. Lafuente-Sanchis, A. Zúñiga & M. Cuenca

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

    A. Olmo, M. Estors-Guerrero, N. J. Martínez-Hernández & J. M. Galbis-Caravajal

  3. Department of Physiology, Facultad de Farmacia, Universidad de Valencia, Valencia, Spain

    J. Carretero

  4. Department of Pathology, Hospital Quirón Valencia, Valencia, Spain

    J. Alcacer Fernandez-Coronado & J. Alcacer

  5. Department of Pathology, Hospital Universitario de la Ribera, Alcira, Spain

    A. Cremades

  6. Laboratory of Oncogenic Signaling, Centro de Investigación Príncipe Felipe, Valencia, Spain

    R. Farras

Authors
  1. A. Lafuente-Sanchis
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  2. A. Olmo
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  8. A. Zúñiga
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  12. J. M. Galbis-Caravajal
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Correspondence to A. Lafuente-Sanchis.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Lafuente-Sanchis, A., Olmo, A., Carretero, J. et al. Clinical significance of epithelial–mesenchymal transition-related markers expression in the micrometastatic sentinel lymph node of NSCLC. Clin Transl Oncol 22, 381–391 (2020). https://doi.org/10.1007/s12094-019-02138-3

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  • DOI: https://doi.org/10.1007/s12094-019-02138-3

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