npj Precision Oncology (Jun 2024)

Molecular landscape and multi-omic measurements of heterogeneity in fetal adenocarcinoma of the lung

  • Li Sun,
  • Wei Guo,
  • Lei Guo,
  • Xiaoxi Chen,
  • Haitao Zhou,
  • Shi Yan,
  • Gang Zhao,
  • Hua Bao,
  • Xue Wu,
  • Yang Shao,
  • Jianming Ying,
  • Lin Lin

DOI
https://doi.org/10.1038/s41698-024-00569-y
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 11

Abstract

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Abstract Fetal adenocarcinoma of the lung (FLAC) is a rare form of lung adenocarcinoma and was divided into high-grade (H-FLAC) and low-grade (L-FLAC) subtypes. Despite the existence of some small case series studies, a comprehensive multi-omics study of FLAC has yet to be undertaken. In this study, we depicted the multi-omics landscapes of this rare lung cancer type by performing multi-regional sampling on 20 FLAC cases. A comparison of multi-omics profiles revealed significant differences between H-FLAC and L-FLAC in a multi-omic landscape. Two subtypes also showed distinct relationships between multi-layer intratumor heterogeneity (ITH). We discovered that a lower genetic ITH was significantly associated with worse recurrence-free survival and overall survival in FLAC patients, whereas higher methylation ITH in H-FLAC patients suggested a short survival. Our findings highlight the complex interplay between genetic and transcriptional heterogeneity in FLAC and suggest that different types of ITH may have distinct implications for patient prognosis.