Spatial Transcriptome‐Wide Profiling of Small Cell Lung Cancer Reveals Intra‐Tumoral Molecular and Subtype Heterogeneity

Abstract: Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid growth and early metastasis and is susceptible to treatment resistance and recurrence. Understanding the intra‐tumoral spatial heterogeneity in SCLC is crucial for improving patient outcomes and clinically relevant subtyping. In this study, a spatial whole transcriptome‐wide analysis of 25 SCLC patients at sub‐histological resolution using GeoMx Digital Spatial Profiling technology is performed. This analysis deciphered intra‐tumoral multi‐regional heterogeneity, characterized by distinct molecular profiles, biological functions, immune features, and molecular subtypes within spatially localized histological regions. Connections between different transcript‐defined intra‐tumoral phenotypes and their impact on patient survival and therapeutic response are also established. Finally, a gene signature, termed ITHtyper, based on the prevalence of intra‐tumoral heterogeneity levels, which enables patient risk stratification from bulk RNA‐seq profiles is identified. The prognostic value of ITHtyper is rigorously validated in independent multicenter patient cohorts. This study introduces a preliminary tumor‐centric, regionally targeted spatial transcriptome resource that sheds light on previously unexplored intra‐tumoral spatial heterogeneity in SCLC. These findings hold promise to improve tumor reclassification and facilitate the development of personalized treatments for SCLC patients.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Spatial Transcriptome‐Wide Profiling of Small Cell Lung Cancer Reveals Intra‐Tumoral Molecular and Subtype Heterogeneity ; day:19 ; month:06 ; year:2024 ; extent:15
Advanced science ; (19.06.2024) (gesamt 15)

Urheber
Zhang, Zicheng
Sun, Xujie
Liu, Yutao
Zhang, Yibo
Yang, Zijian
Dong, Jiyan
Wang, Nan
Ying, Jianming
Zhou, Meng
Yang, Lin

DOI
10.1002/advs.202402716
URN
urn:nbn:de:101:1-2406201422229.728835510259
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
14.08.2025, 11:01 MESZ

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Beteiligte

  • Zhang, Zicheng
  • Sun, Xujie
  • Liu, Yutao
  • Zhang, Yibo
  • Yang, Zijian
  • Dong, Jiyan
  • Wang, Nan
  • Ying, Jianming
  • Zhou, Meng
  • Yang, Lin

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