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Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 3/2020

01-03-2020 | NSCLC | Research Article

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

Published in: Clinical and Translational Oncology | Issue 3/2020

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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.
Appendix
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Literature
1.
Chen W, Zhang S, Zou X. Evaluation on the incidence, mortality and tendency of lung cancer in China. Thorac Cancer. 2010;1:35–40.PubMedCrossRef
2.
Gilmore DM, Khullar OV, Jaklitsch MT, Chirieac LR, Frangioni JV, Colson YL. Identification of metastatic nodal disease in a phase 1 dose-escalation trial of intraoperative sentinel lymph node mapping in non–small cell lung cancer using near-infrared imaging. J Thorac Cardiovasc Surg. 2013;146:562–70.PubMedPubMedCentralCrossRef
3.
4.
Benlloch S, Galbis JM, Alenda C, Peiró FM, Sánchez-Ronco M, Rodríguez-Paniagua JM, et al. Expression of molecular markers in mediastinal nodes from resected stage I non-small cell lung cancer (NSCLC): prognostic impact and potential role as markers of occult micrometastases. Ann Oncol. 2009;20:91–7.PubMedCrossRef
5.
Hanna MG, Jaffer S, Bleiweiss IJ, Nayak A. Re-evaluating the role of sentinel lymph node biopsy in microinvasive breast carcinoma. Mod Pathol. 2014;27(11):1489–98.PubMedCrossRef
6.
Shimazu K, Noguchi S. Clinical significance of breast cancer micrometastasis in the sentinel lymph node. Surg Today. 2016;46(2):155–60.PubMedCrossRef
7.
Aramaki N, Ishii G, Yamada E, Morise M, Aokage K, Kojima M, et al. Drastic morphological and molecular differences between lymph node micrometastatic tumors and macrometastatic tumors of lung adenocarcinoma. J Cancer Res Clin Oncol. 2016;142:37–46.PubMedCrossRef
8.
Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED, et al. Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J Cell Physiol. 2007;213:374–83.PubMedCrossRef
9.
10.
11.
Adam L, Zhong M, Choi W, Qi W, Nicoloso M, Arora A, et al. miR-200 expression regulates epithelial-tomesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy. Clin Cancer Res. 2009;15:5060–72.PubMedPubMedCentralCrossRef
12.
Risolino M, Mandia N, Iavarone F, Dardaei L, Longobardi E, Fernandez S, et al. Transcription factor PREP1 induces EMT and metastasis by controlling the TGF-β–SMAD3 pathway in non-small cell lung adenocarcinoma. PNAS. 2014;111:E3775–E37843784.PubMedCrossRef
13.
Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Wilfried E, et al. The IASLC Lung Cancer Staging Project: proposals for revision of the TNM stage groupings in the forthcoming (Eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2015;11(1):39–51.CrossRef
14.
Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, Yatabe Y, et al. International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244–85.PubMedPubMedCentralCrossRef
15.
Chae YK, Chang S, Ko T, Anker J, Agte S, Iams W, et al. Epithelial-mesenchymal transition (EMT) signature is inversely associated with T-cell infiltration in non-small cell lung cancer (NSCLC). Sci Rep. 2018;8(1):2918.PubMedPubMedCentralCrossRef
16.
Karlsson MC, Gonzalez SF, Welin J, Fuxe J. Molecular Epithelial-mesenchymal transition in cancer metastasis through the lymphatic system. Oncology. 2017;11:781–91.
17.
Markiewicz A, Wełnicka-Jaśkiewicz M, Seroczyńska B, Skokowski J, Majewska H, Szade J, et al. Epithelial-mesenchymal transition markers in lymph node metastases and primary breast tumors - relation to dissemination and proliferation. Am J Transl Res. 2014;6(6):793–808.PubMedPubMedCentral
18.
Toll A, Masferrer E, Hernández-Ruiz ME, Ferrandiz-Pulido C, Yébenes M, Jaka A, et al. Epithelial to mesenchymal transition markers are associated with an increased metastatic risk in primary cutaneous squamous cell carcinomas but are attenuated in lymph node metastases. J Dermatol Sci. 2013;72(2):93–102.PubMedCrossRef
19.
Yusup A, Huji B, Fang C, Wang F, Dadihan T, Wang H, et al. Expression of trefoil factors and TWIST1 in colorectal cancer and their correlation with metastatic potential and prognosis. World J Gastroenterol. 2017;23(1):110–20.PubMedPubMedCentralCrossRef
20.
Blanco MJ, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios JA, et al. Correlation of snail expression with histological grade and lymph node status in breast carcinoma. Oncogene. 2002;21:3241–6.PubMedCrossRef
21.
Maeng YI, Kim KH, Kim JY, Lee SJ, Sung WJ, Lee CK, et al. Transcription factors related to epithelial mesenchymal transition in tumor center and margin in invasive lung adenocarcinoma. Int J Clin Exp Pathol. 2014;7(7):4095–103.PubMedPubMedCentral
22.
Nakamura M, Onoda N, Noda S, Kashiwagi S, Aomatsu N, Kurata K, et al. E-cadherin expression and cell proliferation in the primary tumor and metastatic lymph nodes of papillary thyroid microcarcinoma. Mol Clin Oncol. 2014;2:226–32.PubMedCrossRef
23.
Markiewicz A, Ahrends T, Wełnicka-Jaśkiewicz M, Seroczyńska B, Skokowski J, Jaśkiewicz J, et al. Expression of epithelial to mesenchymal transition-related markers in lymph node metastases as a surrogate for primary tumor metastatic potential in breast cancer. J Transl Med. 2012;10:226.PubMedPubMedCentralCrossRef
24.
Wang G, Dong W, Shen H, Mu X, Li Z, Lin X, et al. A comparison of Twist and E-cadherin protein expression in primary non-small-cell lung carcinoma and corresponding metastases. Eur J Cardiothorac Surg. 2011;39:1028–32.PubMedCrossRef
25.
Wen J, Luo KJ, Liu QW, Wang G, Zhang MF, Xie XY, et al. The epithelial-mesenchymal transition phenotype of metastatic lymph nodes impacts the prognosis of esophageal squamous cell carcinoma patients. Oncotarget. 2016;7(25):37581–8.PubMedPubMedCentralCrossRef
26.
Okubo K, Uenosono Y, Arigami T, Yanagita S, Matsushita D, Kijima T, et al. Clinical significance of altering epithelial–mesenchymal transition in metastatic lymph nodes of gastric cancer. Cancer. 2017;20:802–10.
27.
Tomaszek SC, Kim Y, Cassivi SD, Jensen MR, Shen KH, Nichols FC, et al. Bronchial resection margin length and clinical outcome in non-small cell lung cancer. Eur J Cardiothorac Surg. 2011;40(5):1151–6.PubMed
28.
Maeda R, Yoshida J, Ishii G, Hishida T, Nishimura M, Nagai K. Risk factors for tumor recurrence in patients with early-stage (stage I and II) non-small cell lung cancer: patient selection criteria for adjuvant chemotherapy according to the 7th edition TNM classification. Chest. 2011;140(6):1494–502.PubMedCrossRef
29.
Al-Saad S, Al-Shibli K, Donnem T, Persson M, Bremnes RM, Busund LT. The prognostic impact of NF-kappaB p105, vimentin, E-cadherin and Par6 expression in epithelial and stromal compartment in non-small-cell lung cancer. Br J Cancer. 2008;99:1476–83.PubMedPubMedCentralCrossRef
30.
Ye Z, Zhang X, Luo Y, Li S, Huang L, Li Z, et al. Prognostic Values of vimentin expression and its clinicopathological significance in non- small cell lung cancer: a meta-analysis of observational studies with 4118 cases. PLoS ONE. 2016;11(9):e0163162.PubMedPubMedCentralCrossRef
31.
32.
Kim J, Hong SJ, Park JY, Park JH, Yu Y, Park SY, et al. Epithelial–mesenchymal transition gene signature to predict clinical outcome of hepatocellular carcinoma. Cancer Sci. 2010;101(6):1521–8.PubMedCrossRef
33.
Gibbons DL, Creighton CJ. Pan-cancer survey of epithelial-mesenchymal transition markers across the cancer genome Atlas. Dev Dyn. 2018;247:555–64.PubMedCrossRef
Metadata
Title
Clinical significance of epithelial–mesenchymal transition-related markers expression in the micrometastatic sentinel lymph node of NSCLC
Publication date
01-03-2020
Published in
Clinical and Translational Oncology / Issue 3/2020
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-019-02138-3

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