Department of Pathology, Ajou University School of Medicine, 206 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi, 16499, Republic of Korea.
Department of Thoracic and Cardiovascular Surgery, Ajou University School of Medicine, Suwon, Republic of Korea.
J Cancer Res Clin Oncol. 2019 Jun;145(6):1427-1436. doi: 10.1007/s00432-019-02906-2. Epub 2019 Mar 28.
Cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT) pathways are crucial for cancer progression. However, synergistic interactions between CSC and EMT are not clear in non-small cell lung cancer (NSCLC). The objective of this study was to investigate CSC markers such as CD44, NANOG, and ALDH1 expression and its correlation with EMT markers in NSCLC patients. Its association with survival was also determined.
CD44, NANOG, and ALDH1 protein expression was evaluated in 267 resected NSCLC and its correlation with e-cadherin, β-catenin, p120 catenin, vimentin, SNAIL, and TWIST expressions was determined based on immunohistochemical and mRNA expression data from The Cancer Genome Atlas (TCGA) database. Survival analyses also were performed based on immunohistochemistry and mRNA expression data from Gene Expression Omnibus dataset.
ALDH1 expression in lung adenocarcinoma was positively correlated with the epithelial-like phenotype, low vimentin and low TWIST in immunohistochemical and mRNA expression data. NANOG and ALDH1 expressions measured by immunohistochemical and mRNA expression profiling data of adenocarcinomas were associated with a favorable prognosis. ALDH1 was an independent favorable prognostic marker for overall survival or recurrence-free survival in adenocarcinoma (P = 0.026 and P = 0.033, respectively). The epithelial-like phenotype expressing P120-catenin and beta-catenin was associated with a favorable prognosis; however, the TWIST-expressing mesenchymal-like phenotype was correlated with an unfavorable prognosis.
NANOG and ALDH1 protein or mRNA expression showed improved prognosis in adenocarcinoma alone. ALDH1 expression correlated with an epithelial-like phenotype.
癌症干细胞 (CSC) 和上皮-间充质转化 (EMT) 途径对于癌症的进展至关重要。然而,CSC 与 EMT 之间的协同作用在非小细胞肺癌 (NSCLC) 中并不明确。本研究的目的是研究 NSCLC 患者中 CSC 标志物如 CD44、NANOG 和 ALDH1 的表达及其与 EMT 标志物的相关性,并确定其与生存的关联。
评估了 267 例 NSCLC 患者的 CD44、NANOG 和 ALDH1 蛋白表达,并根据来自癌症基因组图谱 (TCGA) 数据库的免疫组织化学和 mRNA 表达数据,确定其与 E-钙黏蛋白、β-连环蛋白、p120 连环蛋白、波形蛋白、SNAIL 和 TWIST 表达的相关性。还根据基因表达综合数据库的免疫组织化学和 mRNA 表达数据进行了生存分析。
在肺腺癌中,ALDH1 表达与上皮样表型呈正相关,免疫组织化学和 mRNA 表达数据中波形蛋白和 TWIST 低表达。通过免疫组织化学和 mRNA 表达谱数据分析,NANOG 和 ALDH1 在腺癌中的表达与预后良好相关。ALDH1 是腺癌总生存或无复发生存的独立预后良好标志物(P=0.026 和 P=0.033)。表达 P120-连环蛋白和β-连环蛋白的上皮样表型与预后良好相关,而表达 TWIST 的间充质样表型与预后不良相关。
NANOG 和 ALDH1 蛋白或 mRNA 表达在腺癌中单独显示出改善的预后。ALDH1 表达与上皮样表型相关。