Sun Li, Guo Wei, Guo Lei, Chen Xiaoxi, Zhou Haitao, Yan Shi, Zhao Gang, Bao Hua, Wu Xue, Shao Yang, Ying Jianming, Lin Lin
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
NPJ Precis Oncol. 2024 Jun 3;8(1):99. doi: 10.1038/s41698-024-00569-y.
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.
胎儿肺腺癌（FLAC）是肺腺癌的一种罕见形式，分为高级别（H-FLAC）和低级别（L-FLAC）亚型。尽管存在一些小样本病例系列研究，但尚未对FLAC进行全面的多组学研究。在本研究中，我们通过对20例FLAC病例进行多区域采样，描绘了这种罕见肺癌类型的多组学图谱。多组学图谱比较显示，在多组学格局中，H-FLAC和L-FLAC之间存在显著差异。两种亚型在多层肿瘤内异质性（ITH）之间也显示出不同的关系。我们发现，较低的基因ITH与FLAC患者较差的无复发生存率和总生存率显著相关，而H-FLAC患者中较高的甲基化ITH提示生存期较短。我们的研究结果突出了FLAC中基因和转录异质性之间的复杂相互作用，并表明不同类型的ITH可能对患者预后有不同的影响。
