Immunohistochemical analysis of the expression of <scp>E</scp>‐cadherin and <scp>ZEB1</scp> in non‐small cell lung cancer

Matsubara, Daisuke; Kishaba, Yuka; Yoshimoto, Taichiro; Sakuma, Yoshiki; Sakatani, Takashi; Tamura, Tomoko; Endo, Shunsuke; Sugiyama, Yukihiko; Murakami, Yoshinori; Niki, Toshiro

doi:10.1111/pin.12214

Cited by 30 publications

(22 citation statements)

References 20 publications

(21 reference statements)

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“…3a and Supplementary Table 3). Consistent with previous studies [31,32], different tumors demonstrated different epithelial-mesenchymal transition scores and the poorly differentiated large-cell carcinoma, pleomorphic carcinoma, and squamous cell carcinomas showed higher (i.e., more mesenchymal) scores than adenocarcinomas (p value: 0.003). Different regions of the same tumors demonstrated similar epithelial-mesenchymal transition scores for the most part (intraclass correlation coefficient of epithelial-mesenchymal transition score: 0.71, 95% CI (0.43, 0.90)); however, considerable intratumor heterogeneity of epithelial-mesenchymal transition scores were observed in some tumors.…”

Section: Varied Prognostic Gene Signatures Within the Same Tumorssupporting

confidence: 90%

Multiregion gene expression profiling reveals heterogeneity in molecular subtypes and immunotherapy response signatures in lung cancer

et al. 2018

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Intra-tumor heterogeneity may be present at all molecular levels. Genomic intra-tumor heterogeneity at the exome level has been reported in many cancer types, but comprehensive gene expression intra-tumor heterogeneity has not been well studied. Here, we delineated the gene expression intra-tumor heterogeneity by exploring gene expression profiles of 35 tumor regions from 10 non-small cell lung cancer tumors (three or four regions/tumor), including adenocarcinoma, squamous cell carcinoma, large-cell carcinoma, and pleomorphic carcinoma of the lung. Using Affymetrix Gene 1.0 ST arrays, we generated the gene expression data for every sample. Inter-tumor heterogeneity was generally higher than intra-tumor heterogeneity, but some tumors showed a substantial level of intra-tumor heterogeneity. The analysis of various clinically relevant gene expression signatures including molecular subtype, epithelial-to-mesenchymal transition, and anti-PD-1 resistance signatures also revealed heterogeneity between different regions of the same tumor. The gene expression intra-tumor heterogeneity we observed was associated with heterogeneous tumor microenvironments represented by stromal and immune cells infiltrated. Our data suggest that RNA-based prognostic or predictive molecular tests should be carefully conducted in consideration of the gene expression intra-tumor heterogeneity.

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Section: Varied Prognostic Gene Signatures Within the Same Tumorssupporting

confidence: 90%

Multiregion gene expression profiling reveals heterogeneity in molecular subtypes and immunotherapy response signatures in lung cancer

et al. 2018

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“…5,[40][41][42] Due to the pivotal role of ZEB1 in the downregulation of E-cadherin, ZEB1 acts as a driver of EMT and cancer progression. 16,28,33,34,44 Aberrant expression of ZEB1 has been observed in many human cancers, such as uterine cancer, 45 pancreatic cancer, 29,46 osteosarcoma, 47 lung cancer, 48,49 liver cancer, 50 gastric cancer, 51,52 colon cancer 53 and breast cancer. 30 In these tumors, ZEB1 expression correlates with loss of E-cadherin and is associated with advanced diseases or metastasis, which indicates the relevance of ZEB1 induction of EMT and tumor progression in clinical cancers.…”

Section: Zeb1 In Tumor Progressionmentioning

confidence: 99%

ZEB1: At the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance

Zhang¹,

2015

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Zinc finger E-box binding homeobox 1 (ZEB1) is a transcription factor that promotes tumor invasion and metastasis by inducing epithelial-mesenchymal transition (EMT) in carcinoma cells. EMT not only plays an important role in embryonic development and malignant progression, but is also implicated in cancer therapy resistance. It has been hypothesized that carcinoma cells that have undergone EMT acquire cancer stem cell properties including selfrenewal, chemoresistance and radioresistance. However, our recent data indicate that ZEB1 regulates radioresistance in breast cancer cells through an EMT-independent mechanism. In this Perspective, we review different mechanisms by which ZEB1 regulates tumor progression and treatment resistance. Based on studies by us and others, we propose that it is specific EMT inducers like ZEB1, but not the epithelial or mesenchymal state itself, that dictate cancer stem cell properties.

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“…Epithelial-mesenchymal transition is a complicated progress, during which, epithelial cells lose their epithelial features and gain mesenchymal characteristics, and become invasive. As shown by many groups, loss of epithelial marker E-cadherin and gain of mesenchymal markers N-cadherin are usually considered as the molecular markers of EMT (8)(9)(10). Recent studies have shown that many transcription factors are involved in the progress of EMT, such as Snail (11,12).…”

Section: Introductionmentioning

confidence: 99%

Foxk2 inhibits non-small cell lung cancer epithelial-mesenchymal transition and proliferation through the repression of different key target genes

Chen

Jiang

et al. 2017

Oncology Reports

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Increasing evidence suggests that numerous fork-head transcription factors are required to repress the mammalian cells phenotype. Among them, Foxk2 is a ubiquitously expressed family member, but the role of Foxk2 in mediating tumor metastasis in non-small cell lung cancer has not been explored. In this investigation reduced Foxk2 expression was found in lung adenocarcinoma tissues compared with the adjacent non-tumor tissues, and was associated with better overall survival. Low expression was also found in the NSCLC cell lines such as A549, NCI-H520, H1299, H358 and H460 cells. Recombinant lentivirus expressing Foxk2 constructs or ShFoxk2 were developed and transfected into A549 cells or NCI-H520 cells, immunofluorescence assay, qRT-PCR, and western blot analysis were used to measure the change of the epithelial markers, E-cadherin and α-catenin, and mesenchymal markers N-cadherin and vimentin. Wound healing assay and Transwell assay were used to measure the relative cell invasion ability. MTT assay, Edu assay, and cell cycle distribution analysis were used to confirm the effect of Foxk2 on cell proliferation. ChIP-seq, qChIP, as well as luciferase reporter gene assays were used to detect the target genes regulated by Foxk2, Bioinformatics predicated the potential miRNAs that could target Foxk2. Our study demonstrated that Foxk2 played major roles in NSCLC EMT by directly targeting N-cadherin and Snail, we found that Foxk2 regulated NSCLC cell growth by suppressing the expression of cyclin D1 and CDK4, which suggested that Foxk2 might be a multifunctional regulator in NSCLC. The expression of Foxk2 may be regulated by miR-1271, which could serve as a promising therapeutic target for NSCLC.

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Immunohistochemical analysis of the expression of E‐cadherin and ZEB1 in non‐small cell lung cancer

Cited by 30 publications

References 20 publications

Multiregion gene expression profiling reveals heterogeneity in molecular subtypes and immunotherapy response signatures in lung cancer

Multiregion gene expression profiling reveals heterogeneity in molecular subtypes and immunotherapy response signatures in lung cancer

ZEB1: At the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance

Foxk2 inhibits non-small cell lung cancer epithelial-mesenchymal transition and proliferation through the repression of different key target genes

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