Evidence map›Paper›PMID 42860723›Full record

ArticleCancer science2026

Spatial Atlas of Small Cell Lung Carcinoma Reveals Intratumoral Tumor-State Heterogeneity and an MMP12

Naozane Nomura, Naoe Jimbo, Takaaki Nakanishi, Yukinobu Ito, Maki Sakaguchi, Daichi Maeda, Hiroko Ikeda, Tsukasa Ueda, Hayato Koba, Seiji Yano and 6 more

Abstract read
In one paragraph

Article in Cancer science, 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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0cells of the map it votes in
0citing papers in PubMed
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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

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.

Naozane NomuraDivision of Molecular and Genomic Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.ORCID https://orcid.org/0009-0007-0700-058X
Naoe JimboDivision of Molecular and Genomic Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.ORCID https://orcid.org/0000-0003-0423-3568
Takaaki NakanishiDivision of Molecular and Genomic Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.
Yukinobu ItoDepartment of Molecular and Cellular Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Maki SakaguchiDepartment of Molecular and Cellular Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Daichi MaedaDivision of Molecular and Genomic Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.
Hiroko IkedaDepartment of Diagnostic Pathology, Kanazawa University Hospital, Kanazawa, Japan.
Tsukasa UedaDepartment of Respiratory Medicine, Kanazawa University Hospital, Kanazawa, Japan.
Hayato KobaDepartment of Respiratory Medicine, Kanazawa University Hospital, Kanazawa, Japan.
Seiji YanoDepartment of Respiratory Medicine, Kanazawa University Hospital, Kanazawa, Japan.ORCID https://orcid.org/0000-0002-6151-2988
Isao MatsumotoDepartment of Thoracic Surgery, Kanazawa University, Kanazawa, Japan.
Patrick MickeDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Takayuki KodamaDivision of Molecular and Genomic Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.
Manabu ShigeokaDivision of Molecular and Genomic Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.
Yu-Ichiro KomaDivision of Molecular and Genomic Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.ORCID https://orcid.org/0000-0002-3022-8466
Masafumi HorieDivision of Molecular and Genomic Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.

Funding

Japan Agency for Medical Research and Development JP256f0137011Japan Society for the Promotion of Science 23K07649Kobayashi Foundation for Cancer ResearchTakeda Science FoundationThe Japan Lung Cancer Society
6 · The paper itself

Abstract

Small-cell lung carcinoma (SCLC) is a highly aggressive tumor with a dismal prognosis among lung cancers. Treatment is failing because of primary or rapidly developing secondary resistance. Recent molecular studies have suggested four SCLC subtypes with unique therapeutic vulnerabilities-ASCL1, NEUROD1, POU2F3, and YAP. These subtypes still distinguish themselves by considerable intra-tumoral heterogeneity and the influence of the microenvironmental context, which are both considered to be responsible for treatment resistance. We integrated in situ hybridization-based spatial transcriptomics with histological and protein-expression analyses of 18 specimens, comprising 16 SCLCs, one atypical carcinoid, and one normal lung specimen. Systematic case-by-case analysis revealed multiple coexisting tumor states, including neuroendocrine and non-neuroendocrine components, regional hypoxic states, and case-specific FABP7-positive and loss-of-chromosome-Y-associated populations. Integrative transcriptome clustering, copy number estimation, and exploratory trajectory analysis revealed transcriptional relationships among spatially coexisting tumor states, including phenotypically distinct tumor components with molecular features consistent with close clonal relationships in selected heterogeneous tumors. Furthermore, we identified immune signatures and uncovered a previously unrecognized MMP12-positive tumor-associated macrophage population, enriched at the tumor interface and spatially associated with necrotic and hypoxic regions. In vitro co-culture experiments further showed that direct contact with SCLC cells increased MMP12 expression in macrophages, with hypoxia further enhancing its expression under specific conditions. Together, our study delineates the complex spatial architecture of SCLC by defining specific cellular programs and adjacent immune phenotypes that provide an organizational framework for understanding its marked intratumoral heterogeneity.

Indexed as

lung neoplasmsmacrophagessmall cell carcinomatranscriptometumor microenvironment

Identifiers

PMID42860723
PMCPMC13655396

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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.