Saygideger Yasemin, Avci Alper, Bagir Emine, Saygıdeğer Demir Burcu, Sezan Aycan, Ekici Mucahit, Baydar Oya, Erkin Özgür Cem
Department of Pulmonary, Cukurova University School of Medicine, Adana, Turkey.
Institute of Health Sciences, Department of Translational Medicine, Cukurova University, Adana, Turkey.
Discov Oncol. 2022 Jan 22;13(1):7. doi: 10.1007/s12672-022-00467-4.
Lung 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.
Eighty-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.
Skip-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.
The results indicate that, at molecular level, Skip N2 pathogenesis has different molecular background and regulation of SLUG expression may orchestrate the process.
肺癌在肿瘤本身及其转移区域均表现出异质性。肿瘤的一种有趣行为被称为跳跃性N2转移，即N2淋巴结含有肿瘤细胞而N1淋巴结无肿瘤细胞。在本研究中，调查了非小细胞肺癌组织中跳跃性N2转移和正常N2转移中上皮-间质转化（EMT）相关基因的mRNA水平，以评估可能导致跳跃性N2转移发病机制的分子背景。
本研究分析了83例手术切除并石蜡包埋的肺癌患者淋巴结样本，其中40例为跳跃性N2转移。从含50%肿瘤的区域采集N2组织样本并提取总RNA。通过qPCR分析18S、E-钙黏蛋白、波形蛋白、锌指蛋白1（ZEB1）和蜗牛蛋白（SLUG）的mRNA水平，通过免疫组织化学（IHC）分析E-钙黏蛋白和波形蛋白的蛋白水平。采用生物信息学分析在线数据集，以评估肺癌组织样本中与SLUG显著共表达的基因。
腺癌亚型的跳跃性N2转移患者生存率更高。PCR结果的比较分析表明，跳跃性N2转移肿瘤组织的E-钙黏蛋白/波形蛋白比值和ZEB1 mRNA表达增加，SLUG水平显著降低。跳跃性N2转移中E-钙黏蛋白的IHC染色较高，非跳跃性N2转移中波形蛋白的IHC染色较高。在生物信息学分析中，TP63与SLUG表达密切相关。
结果表明，在分子水平上，跳跃性N2转移的发病机制具有不同的分子背景，SLUG表达的调控可能参与了这一过程。
