論文 - 詳細
| RRC ID | 75019 |
|---|---|
| 著者 | Matsubara D, Yoshimoto T, Soda M, Amano Y, Kihara A, Funaki T, Ito T, Sakuma Y, Shibano T, Endo S, Hagiwara K, Ishikawa S, Fukayama M, Murakami Y, Mano H, Niki T. |
| タイトル | Reciprocal expression of trefoil factor-1 and thyroid transcription factor-1 in lung adenocarcinomas. |
| ジャーナル | Cancer Sci |
| 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. |
| 巻・号 | 111(6) |
| ページ | 2183-2195 |
| 公開日 | 2020-6-1 |
| DOI | 10.1111/cas.14403 |
| PMID | 32237253 |
| PMC | PMC7293082 |
| MeSH | Adenocarcinoma of Lung / classification Adenocarcinoma of Lung / metabolism* Adenocarcinoma of Lung / pathology Adult Aged Aged, 80 and over Biomarkers, Tumor / analysis Biomarkers, Tumor / metabolism Cell Line, Tumor Female Humans Lung Neoplasms / classification Lung Neoplasms / metabolism* Lung Neoplasms / pathology Male Middle Aged Thyroid Nuclear Factor 1 / metabolism* Trefoil Factor-1 / metabolism* |
| IF | 4.966 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |