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Reciprocal expression of TFF-1 (trefoil factor-1) and TTF-1 (thyroid transcription factor-1) in lung adenocarcinomas.

肺腺癌中 TFF-1 (三叶因子-1) 和 TTF-1 (甲状腺转录因子-1) 的相互表达。

  • 影响因子:4.60
  • DOI:10.1111/cas.14403
  • 作者列表:"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
  • 发表时间:2020-04-01
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 TTF-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%). TFF-1 expression 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%). TFF-1 expression correlated with the expression of HNF4alpha and MUC5AC (p<0.0001, p<0.0001, respectively) and inversely correlated with that of TTF-1/NKX2-1 (p<0.0001). These results indicate that TFF-1 is characteristically expressed in non-TRU-type adenocarcinomas with gastrointestinal features. TFF-1-positive cases harbored KRAS mutations at a high frequency, but no EGFR or ALK mutations. TFF-1 expression correlated with tumor spread through air space (STAS), 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.

摘要

: 针对 EGFR 和 ALK 的分子靶向治疗改善了肺腺癌患者的生活质量。然而,可靶向驱动突变主要见于 TTF-1/NKX2-1-positive 末端呼吸单位 (TRU) 类型,而非 TRU 类型很少。为了阐明非 TRU 型腺癌主要亚型的分子特征,我们分析了 19 个肺腺癌细胞系 (11 个 TRU 型和 8 个非 TRU 型)。非 TRU 型细胞系的一个特点是强表达胃粘膜保护因子 TFF-1 (三叶因子-1)。对吉奇医科大学医院切除的 238 例原发性肺腺癌进行免疫组织化学分析,发现 31 例 (13%) TFF-1 阳性。TFF-1 在浸润性粘液性腺癌 (14/15,93%) 、肠道腺癌 (2/2,100%) 和胶质腺癌 (1/1,100%) 中频繁检测到,在腺泡状腺癌 (5/24,21%) 中较少见。乳头状 (7/120,6% ), 和实性 (2/43,5%) 腺癌,微乳头状 (0/1,0% ), lepidic(0/23,0% ), 和微浸润腺癌或原位腺癌 (0/9,0%)。TFF-1 与 hnf4 α 和 MUC5AC 的表达呈正相关 (p<0.0001,p<0.0001),与 TTF-1/NKX2-1 的表达呈负相关 (p<0.0001)。这些结果表明,TFF-1 在具有胃肠道特征的非 TRU 型腺癌中特征性表达。TFF-1-positive 病例存在高频率的 KRAS 突变,但无 EGFR 或 ALK 突变。TFF-1 表达与肿瘤通过空气间隙扩散 (STAS) 相关,晚期预后较差。此外,在 TFF-1 和 KRAS 突变的肺腺癌细胞系中,TFF-1-high 的敲除抑制细胞增殖和软琼脂集落形成并诱导细胞凋亡。这些结果表明,TFF-1 不仅是生物标志物,而且是非 TRU 型肺腺癌的潜在分子靶点。

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影响因子:4.88
发表时间:2020-03-01
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作者列表:["Suvina V","Kokulnathan T","Wang TJ","Balakrishna RG"]

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影响因子:6.50
发表时间:2020-03-31
来源期刊:Cancer letters
DOI:10.1016/j.canlet.2019.12.039
作者列表:["Zhou Z","Zhou Q","Wu X","Xu S","Hu X","Tao X","Li B","Peng J","Li D","Shen L","Cao Y","Yang L"]

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