Abstract
ObjectiveLung cancer displays heterogeneity both in the tumor itself and in its metastatic regions. One interesting behavior of the tumor is known as Skip N2 metastasis, which N2 lymph nodes contain tumor cells while N1 are clean. In this study, mRNA levels of epithelial mesenchymal transition (EMT) related genes in skip N2 and normal N2 involvements of non-small cell lung cancer tissues were investigated to evaluate the possible molecular background that may contribute to the pathogenesis of Skip N2 metastasis.Materials and methodsEighty-three surgically resected and paraffin embedded lymph node samples of lung cancer patients were analyzed in this study, which 40 of them were Skip N2. N2 tissues were sampled from 50% tumor containing areas and total RNA was extracted. mRNA levels for 18S, E-cadherin, Vimentin, ZEB1 and SLUG were analyzed via qPCR and E-cadherin and vimentin protein levels via immunohistochemistry (IHC). Bioinformatic analysis were adopted using online datasets to evaluate significantly co-expressed genes with SLUG in lung cancer tissue samples.ResultsSkip-N2 patients who had adenocarcinoma subtype had better survival rates. Comparative analysis of PCR results indicated that Skip N2 tumor tissues had increased E-Cadherin/Vimentin ratio and ZEB1 mRNA expression, and significantly decreased levels of SLUG. E-cadherin IHC staining were higher in Skip N2 and Vimentin were in Non-Skip N2. TP63 had a strong correlation with SLUG expression in the bioinformatics analyses.ConclusionThe results indicate that, at molecular level, Skip N2 pathogenesis has different molecular background and regulation of SLUG expression may orchestrate the process.
Highlights
Lung Cancer, which ranks first in cancer-related deaths in the world, is being investigated intensively with studies based on advances in molecular biology and technology
We aimed to evaluate the expression levels of epithelial cell marker E-Cadherin and mesenchymal cell markers Vimentin, ZEB1 and SNAI2 (SLUG) mRNA levels in surgically resected and paraffin embedded lymph node samples of lung cancer patients and to compare the overall survival rates of the lung cancer patients with Skip N2 and normal N2 metastasis
MRNA levels of epithelial mesenchymal transition (EMT)-related genes ECAD, VIM, ZEB1, SLUG was evaluated in Skip N2 metastasis, which is a common entity in the lymphatic spread of the tumor in lung cancer patients and the molecular mechanism has not yet been elucidated
Summary
Lung Cancer, which ranks first in cancer-related deaths in the world, is being investigated intensively with studies based on advances in molecular biology and technology. Lung cancers generally show intra-tumoral heterogeneity and use adaptation and resistance mechanisms extensively. In this case, targeted therapies and close monitoring and understanding of the adaptive response and resistance mechanisms developed by the tumor play an important role in the fight against this cancer. Development of targeted therapies is possible by getting to know the biological behavior of cancers closely. Lung cancers are histologically divided into 2 main subtypes: Non-Small Cell Lung Cancers (NSCLC) and neuroendocrine tumors. T = tumor size, N = lymph node involvement and M = metastasis. Lymph node metastasis is important in lung cancer staging. N1: Involvement in the same sided peri bronchial and hilar lymph nodes, N2: Involvement in the mediastinal or subcarinal lymph nodes on the same side, N3 refers to involvement in the contralateral mediastinal, hilar, or the same/opposite sided scalene or supraclavicular lymph nodes [1]
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