Evidence map›Paper›PMID 40898302›Full record

ArticleGenome medicine2025

Deep learning-based histomorphological subtyping and risk stratification of small cell lung cancer from hematoxylin and eosin-stained whole slide images.

Yibo Zhang, Shilong Liu, Jun Chen, Ruanqi Chen, Zijian Yang, Ruyu Sheng, Xin Li, Taolue Wang, Hongyu Liu, Fan Yang and 4 more

Abstract read
In one paragraph

Article in Genome medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026
    Review
  7. Review
  8. Review
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

14 authors.

Yibo Zhang *School of Biomedical Engineering, Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China.
Shilong Liu *Department of Thoracic Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, People's Republic of China.
Jun Chen *Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, 300041, People's Republic of China.
Ruanqi ChenDepartment of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China.
Zijian YangSchool of Biomedical Engineering, Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China.
Ruyu ShengSchool of Biomedical Engineering, Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China.
Xin LiSchool of Biomedical Engineering, Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China.
Taolue WangSchool of Biomedical Engineering, Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China.
Hongyu LiuDepartment of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, 300041, People's Republic of China.
Fan YangDepartment of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China.
Jianming YingDepartment of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China. jmying@cicams.ac.cn.
Lin YangDepartment of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China. yanglin@cicams.ac.cn.
Jie SunSchool of Biomedical Engineering, Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China. suncarajie@wmu.edu.cn.
Meng ZhouSchool of Biomedical Engineering, Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China. zhoumeng@wmu.edu.cn.

Funding

CAMS Innovation Fund for Medical Sciences 2024-I2M-C&T-A-005National High Level Hospital Clinical Research Funding C2024L01
6 · The paper itself

Abstract

backgroundAccurate subtyping and risk stratification are imperative for prognostication and clinical decision-making in small cell lung cancer (SCLC). However, traditional molecular subtyping is resource-intensive and challenging to translate into clinical practice.

methodsA total of 517 SCLC patients and their corresponding hematoxylin and eosin (H&E)-stained whole slide images (WSIs) from three independent medical institutions were analyzed. A hybrid clustering-based unsupervised deep representation learning model was developed to identify histomorphological phenotypes (HIPO) and characterize tumor ecosystem diversity. Consensus clustering and a deep learning-based stratification system were used to define histomorphological subtypes (HIPOS) based on patient-level HIPO features. Survival analysis and Cox proportional hazards regression models were used to assess the clinical significance of HIPOS. An integrated analysis of pathomics, proteomics, and immunohistochemistry was conducted to explore the biological and microenvironmental correlates of HIPOS.

resultsWe performed histomorphological phenotyping of SCLC using unsupervised deep representation learning from WSIs and identified 15 HIPOs. Unsupervised clustering of HIPO profiles stratified SCLCs into two reproducible image-based subtypes: HIPOS-I and HIPOS-II. Patients in the HIPOS-I group had better overall survival and disease-free survival compared to those in HIPOS-II, independent of clinical features and molecular subtypes. Multimodal analyses revealed that HIPOS-I tumors were characterized by enriched immune infiltration and immune activation, whereas HIPOS-II tumors displayed increased fibrosis, cellular pleomorphism, and dysregulated oxidative metabolism. Additionally, we developed a simplified deep-learning model to predict HIPOS subtypes to enhance clinical applications and validated the prognostic value of these subtypes in independent cohorts.

conclusionsThis study demonstrates the potential of a deep learning-based histomorphological subtyping system to improve patient stratification and prognosis prediction in SCLC. The HIPOS offers a promising and clinically applicable tool for personalized management using routine H&E-stained WSIs.

Indexed as

Deep LearningLung NeoplasmsSmall Cell Lung CarcinomaAgedEosine Yellowish-(YS)FemaleHematoxylinHumansMaleMiddle AgedPrognosisRisk AssessmentTumor MicroenvironmentEosine Yellowish-(YS)HematoxylinDeep learningHistomorphological subtypingRisk stratificationSmall cell lung cancerWhole slide images

Identifiers

PMID40898302
PMCPMC12406473

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.