Evidence map›Paper›PMID 32237253›Full record

ArticleCancer science2020

Reciprocal expression of trefoil factor-1 and thyroid transcription factor-1 in lung adenocarcinomas.

Daisuke Matsubara, Taichiro Yoshimoto, Manabu Soda, Yusuke Amano, Atsushi Kihara, Toko Funaki, Takeshi Ito, Yuji Sakuma, Tomoki Shibano, Shunsuke Endo and 6 more

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.9field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 19 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 1 country.

Daisuke MatsubaraDivision of Integrative Pathology, Jichi Medical University, Shimotsuke, Japan.ORCID https://orcid.org/0000-0002-6233-6840
Taichiro YoshimotoDivision of Integrative Pathology, Jichi Medical University, Shimotsuke, Japan.ORCID https://orcid.org/0000-0002-4714-5261
Manabu SodaDepartment of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yusuke AmanoDivision of Integrative Pathology, Jichi Medical University, Shimotsuke, Japan.
Atsushi KiharaDivision of Integrative Pathology, Jichi Medical University, Shimotsuke, Japan.
Toko FunakiDivision of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Takeshi ItoDivision of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yuji SakumaDivision of Integrative Pathology, Jichi Medical University, Shimotsuke, Japan.
Tomoki ShibanoDepartment of Thoracic Surgery, Jichi Medical University, Shimotsuke, Japan.
Shunsuke EndoDepartment of Thoracic Surgery, Jichi Medical University, Shimotsuke, Japan.
Koichi HagiwaraDepartment of Respiratory Medicine, Jichi Medical University, Shimotsuke, Japan.
Shumpei IshikawaDepartment of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Masashi FukayamaHuman Pathology Department, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yoshinori MurakamiDivision of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0002-2826-4396
Hiroyuki ManoDivision of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.
Toshiro NikiDivision of Integrative Pathology, Jichi Medical University, Shimotsuke, Japan.
Jichi Medical University · JPThe University of Tokyo · JPTokyo Medical and Dental University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Adenocarcinoma of LungAdultAgedAged, 80 and overBiomarkers, TumorCell Line, TumorFemaleHumansLung NeoplasmsMaleMiddle AgedThyroid Nuclear Factor 1Trefoil Factor-1Biomarkers, TumorNKX2-1 protein, humanTFF1 protein, humanThyroid Nuclear Factor 1Trefoil Factor-1lung adenocarcinomamucinous adenocarcinomanon-TRU typeTFF-1TTF-1

Identifiers

PMID32237253
PMCPMC7293082
OpenAlexW3014291334

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.