Evidence map›Paper›PMID 42581019›Full record

ArticleCancer reports (Hoboken, N.J.)2026

SMAD4 Expression and Its Association With Treatment Resistance and Clinical Outcomes in Oral Squamous Cell Carcinoma Treated With Preoperative Chemoradiotherapy.

Junki Sakata, Akiyuki Hirosue, Ryoji Yoshida, Yuichiro Matsuoka, Yusei Todoroki, Hidetaka Arita, Hikaru Nakashima, Tatsuro Yamamoto, Nozomu Takahashi, Masatoshi Hirayama and 6 more

Abstract read
In one paragraph

Article in Cancer reports (Hoboken, N.J.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Junki SakataDepartment of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.ORCID 0000-0002-5190-8663
Akiyuki HirosueDepartment of Oral and Maxillofacial Surgery, Jichi Medical University, Tochigi, Japan.ORCID 0000-0002-2701-6462
Ryoji YoshidaDepartment of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.ORCID 0000-0002-2317-384X
Yuichiro MatsuokaDivision of Oral and Maxillofacial Surgery, Tsuruta Hospital, Kumamoto, Japan.
Yusei TodorokiDepartment of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Hidetaka AritaSection of Oral Oncology, Fukuoka Dental College, Fukuoka, Japan.
Hikaru NakashimaDepartment of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.ORCID 0000-0003-3225-2336
Tatsuro YamamotoDepartment of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.ORCID 0009-0007-7604-2011
Nozomu TakahashiDivision of Oral and Maxillofacial Surgery, Ariake Medical Center, Arao, Japan.
Masatoshi HirayamaDepartment of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Kenta KawaharaDepartment of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.ORCID 0000-0002-1407-4866
Ryo ToyaDepartment of Radiological Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.ORCID 0000-0001-9764-5718
Ryuji MurakamiDepartment of Medical Imaging, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Takaaki ItoKumamoto Health Science University, Kumamoto, Japan.ORCID 0000-0001-5528-3464
Yoshikazu KuwaharaRadiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Hideki NakayamaDepartment of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.ORCID 0000-0002-3244-0268

Funding

JSPS KAKENHI JP19K21413JSPS KAKENHI JP20K18700
6 · The paper itself

Abstract

backgroundSmall mothers against decapentaplegic homologue 4 (SMAD4) plays an important role in transforming growth factor (TGF)-β signaling and is associated with various cancers. However, little is known about SMAD4 expression in oral squamous cell carcinoma (OSCC).

aimTo investigate the clinical and biological significance of SMAD4 expression in OSCC. METHODS AND

resultsImmunohistochemical analysis was performed to detect SMAD4 expression in 90 OSCC specimens obtained from patients who underwent preoperative chemoradiotherapy and surgery (phase II study). We also investigated the correlation between SMAD4 expression and various clinicopathological features. In vitro experiments were performed to assess the effects of SMAD4 expression on chemosensitivity and changes in apoptosis-related molecules. Notably, low SMAD4 expression was significantly correlated with an increased risk of lymph node metastasis, poor response to chemoradiotherapy, and adverse prognosis in patients with OSCC who underwent preoperative 5-FU-based chemoradiotherapy. Additionally, SMAD4 downregulation in OSCC cells decreased sensitivity to cisplatin and 5-fluorouracil and was associated with an increase in cIAP2 expression.

conclusionThe reduced expression of SMAD4 has been linked to both chemotherapy resistance and prognosis in OSCC. However, it may not function as an independent prognostic biomarker. Further research is necessary to determine whether these findings can be generalized to the broader OSCC population.

Indexed as

Carcinoma, Squamous CellDrug Resistance, NeoplasmMouth NeoplasmsSmad4 ProteinAdultAgedApoptosisBiomarkers, TumorCell Line, TumorChemoradiotherapyCisplatinFemaleFluorouracilHumansLymphatic MetastasisMaleBiomarkers, TumorCisplatinFluorouracilSmad4 ProteinSMAD4 protein, humanapoptosischemoresistanceoral squamous cell carcinomaSMAD4therapeutic resistance

Identifiers

PMID42581019
PMCPMC13461526

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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.