ArticleCancer science2020
Reciprocal expression of trefoil factor-1 and thyroid transcription factor-1 in lung adenocarcinomas.
Article in Cancer science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Integrating multi-omics data revealing LIMK1 as a metastatic biomarker in LUAD patients with brain metastasis.Cancer cell international · 2026Article
- A Transcriptomic Analysis of Cancer-Stromal Interactome in Lung Cancer Xenograft Models.Cancer science · 2026Article
- Expression patterns of HNF4α, TTF-1, and SMARCA4 in lung adenocarcinomas: impacts on clinicopathological and genetic features.Virchows Archiv : an international journal of pathology · 2025Article
- Spatial analyses revealed S100P + TFF1 + tumor cells in spread through air spaces samples correlated with undesirable therapy response in non-small cell lung cancer.Journal of translational medicine · 2024Article
- Expression of Trefoil Factor 1 (TFF1) in Cancer: A Tissue Microarray Study Involving 18,878 Tumors.Diagnostics (Basel, Switzerland) · 2024Article
- Differential diagnosis of Huntington's disease- neurological aspects of NKX2-1-related disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Impact of Results of TTF-1 Immunostaining on Efficacy of Platinum-Doublet Chemotherapy in Japanese Patients with Nonsquamous Non-Small-Cell Lung Cancer.Journal of clinical medicine · 2022Article
- Mechanisms of Dendrobium officinale polysaccharides in repairing gastric mucosal injuries based on mitogen-activated protein kinases (MAPK) signaling pathway.Bioengineered · 2022Article
- Thyroid Transcription Factor-1: Structure, Expression, Function and Its Relationship with Disease.BioMed research international · 2021Review
- TFF-1 Functions to Suppress Multiple Phenotypes Associated with Lung Cancer Progression.OncoTargets and therapy · 2021Article
- [Analysis of Correlation between TTF-1 and Sensitivity to First-line Chemotherapy and Prognosis in Patients with Small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2020Article
- Reciprocal expression of trefoil factor-1 and thyroid transcription factor-1 in lung adenocarcinomas.Cancer science · 2020Article
- Prognostic Value of Gastrokine-2 (GKN2) and Its Correlation with Tumor-Infiltrating Immune Cells in Lung Cancer and Gastric Cancers.Journal of inflammation research · 2020Article
- Relationship Between TTF-1 Expression and PFS of Pemetrexed-containing Chemotherapy in Non-squamous-NSCLC Patients With and Without Driver Genes.Cancer diagnosis & prognosisArticle
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecular targeted therapies against EGFR and ALK have improved the quality of life of lung adenocarcinoma patients. However, targetable driver mutations are mainly found in thyroid transcription factor-1 (TTF-1)/NK2 homeobox 1 (NKX2-1)-positive terminal respiratory unit (TRU) types and rarely in non-TRU types. To elucidate the molecular characteristics of the major subtypes of non-TRU-type adenocarcinomas, we analyzed 19 lung adenocarcinoma cell lines (11 TRU types and 8 non-TRU types). A characteristic of non-TRU-type cell lines was the strong expression of TFF-1 (trefoil factor-1), a gastric mucosal protective factor. An immunohistochemical analysis of 238 primary lung adenocarcinomas resected at Jichi Medical University Hospital revealed that TFF-1 was positive in 31 cases (13%). Expression of TFF-1 was frequently detected in invasive mucinous (14/15, 93%), enteric (2/2, 100%), and colloid (1/1, 100%) adenocarcinomas, less frequent in acinar (5/24, 21%), papillary (7/120, 6%), and solid (2/43, 5%) adenocarcinomas, and negative in micropapillary (0/1, 0%), lepidic (0/23, 0%), and microinvasive adenocarcinomas or adenocarcinoma in situ (0/9, 0%). Expression of TFF-1 correlated with the expression of HNF4-α and MUC5AC (P < .0001, P < .0001, respectively) and inversely correlated with that of TTF-1/NKX2-1 (P < .0001). These results indicate that TFF-1 is characteristically expressed in non-TRU-type adenocarcinomas with gastrointestinal features. The TFF-1-positive cases harbored KRAS mutations at a high frequency, but no EGFR or ALK mutations. Expression of TFF-1 correlated with tumor spread through air spaces, and a poor prognosis in advanced stages. Moreover, the knockdown of TFF-1 inhibited cell proliferation and soft-agar colony formation and induced apoptosis in a TFF-1-high and KRAS-mutated lung adenocarcinoma cell line. These results indicate that TFF-1 is not only a biomarker, but also a potential molecular target for non-TRU-type lung adenocarcinomas.
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