Evidence map›Paper›PMID 38710944›Full record

ArticleVirchows Archiv : an international journal of pathology2025

Expression patterns of HNF4α, TTF-1, and SMARCA4 in lung adenocarcinomas: impacts on clinicopathological and genetic features.

Hitomi Kawai, Tamaki Miura, Natsumi Kawamatsu, Tomoki Nakagawa, Aya Shiba-Ishii, Taichiro Yoshimoto, Yusuke Amano, Atsushi Kihara, Yuji Sakuma, Kazutaka Fujita and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Virchows Archiv : an international journal of pathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. The role of HNF4α in adenocarcinoma.Biochemical Society transactions · 2026
    Review
  4. Article
  5. Article
  6. Article
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

19 authors.

Hitomi KawaiDepartment of Pathology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan.
Tamaki MiuraDepartment of Integrative Pathology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
Natsumi KawamatsuDepartment of Pathology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan.
Tomoki NakagawaDepartment of Diagnostic Pathology, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan.
Aya Shiba-IshiiDepartment of Pathology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan.
Taichiro YoshimotoDepartment of Pathology, Showa General Hospital, 8-1-1 Hanakoganei, Kodaira-Shi, Tokyo, 187-851, Japan.
Yusuke AmanoDepartment of Integrative Pathology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
Atsushi KiharaDepartment of Integrative Pathology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
Yuji SakumaDepartment of Molecular Medicine, Sapporo Medical University, 1-17, Minami Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan.
Kazutaka FujitaDepartment of Respiratory Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan.
Tomoki ShibanoDepartment of Thoracic Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan.
Shumpei IshikawaDepartment of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.
Tetsuo UshikuHuman Pathology Department, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.
Masashi FukayamaHuman Pathology Department, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.
Hiroyoshi TsubochiDepartment of Thoracic Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan.
Shunsuke EndoDepartment of Thoracic Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan.
Koichi HagiwaraOmiya Medical Association Medical Examination Center, 2-107, Higashioonari-Chou, Kita-Ku, Saitama-Shi, Saitama, 331-8689, Japan.
Daisuke MatsubaraDepartment of Pathology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan. matsubarad@md.tsukuba.ac.jp.ORCID http://orcid.org/0000-0002-6233-6840
Toshiro NikiDepartment of Integrative Pathology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.

Funding

Japan Society for the Promotion of Science 17K15652Japan Society for the Promotion of Science 18H02634Japan Society for the Promotion of Science 19K07441Japan Society for the Promotion of Science 22H02840Japan Society for the Promotion of Science 23K06470Japan Society for the Promotion of Science 23K14469
6 · The paper itself

Abstract

introductionHNF4α expression and SMARCA4 loss were thought to be features of non-terminal respiratory unit (TRU)-type lung adenocarcinomas, but their relationships remained unclear. MATERIALS AND

methodsHNF4α-positive cases among 241 lung adenocarcinomas were stratified based on TTF-1 and SMARCA4 expressions, histological subtypes, and driver mutations. Immunohistochemical analysis was performed using xenograft tumors of lung adenocarcinoma cell lines with high HNF4A expression.

resultHNF4α-positive adenocarcinomas(n = 33) were divided into two groups: the variant group(15 mucinous, 2 enteric, and 1 colloid), where SMARCA4 was retained in all cases, and the conventional non-mucinous group(6 papillary, 5 solid, and 4 acinar), where SMARCA4 was lost in 3/15 cases(20%). All variant cases were negative for TTF-1 and showed wild-type EGFR and frequent KRAS mutations(10/18, 56%). The non-mucinous group was further divided into two groups: TRU-type(n = 7), which was positive for TTF-1 and showed predominantly papillary histology(6/7, 86%) and EGFR mutations(3/7, 43%), and non-TRU-type(n = 8), which was negative for TTF-1, showed frequent loss of SMARCA4(2/8, 25%) and predominantly solid histology(4/8, 50%), and never harbored EGFR mutations. Survival analysis of 230 cases based on histological grading and HNF4α expression revealed that HNF4α-positive poorly differentiated (grade 3) adenocarcinoma showed the worst prognosis. Among 39 cell lines, A549 showed the highest level of HNF4A, immunohistochemically HNF4α expression positive and SMARCA4 lost, and exhibited non-mucinous, high-grade morphology in xenograft tumors.

conclusionHNF4α-positive non-mucinous adenocarcinomas included TRU-type and non-TRU-type cases; the latter tended to exhibit the high-grade phenotype with frequent loss of SMARCA4, and A549 was a representative cell line.

Indexed as

AdenocarcinomaAdenocarcinoma of LungBiomarkers, TumorDNA-Binding ProteinsDNA HelicasesHepatocyte Nuclear Factor 4Lung NeoplasmsNuclear ProteinsTranscription FactorsAdultAgedAged, 80 and overAnimalsCell Line, TumorFemaleHumansBiomarkers, TumorDNA-Binding ProteinsDNA HelicasesHepatocyte Nuclear Factor 4HNF4A protein, humanNuclear ProteinsSMARCA4 protein, humanTranscription FactorsTTF1 protein, humanA549HNF4αKRASLung adenocarcinomaSMARCA4TTF-1

Identifiers

PMID38710944
PMCPMC11876232

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.