期刊
CANCER DISCOVERY
卷 11, 期 6, 页码 1490-1507出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-20-1274
关键词
-
类别
资金
- Gabriella Giorgi-Cavaglieri foundation
- University of Lausanne Interdisciplinary Research Grant
- Swiss National Science Foundation (SNSF) [310030_169519]
- Emma Muschamp foundation
- Swiss National Science Foundation (SNF) [310030_169519] Funding Source: Swiss National Science Foundation (SNF)
This study provides a detailed molecular map of intratumor spatial heterogeneity in lung adenocarcinoma, revealing non-genetic routes of cancer evolution. The transition from indolent to aggressive patterns in tumors is driven by epigenetic and transcriptional reprogramming reshaping cancer cell identity rather than genetic alterations. Highly multiplexed protein spatial profiling shows the coexistence of immune desert, inflamed, and excluded regions within individual tumors, matching histologic pattern composition.
Cancer evolution determines molecular and morphologic intratumor heterogeneity and challenges the design of effective treatments. In lung adenocarcinoma, disease progression and prognosis are associated with the appearance of morphologically diverse tumor regions, termed histologic patterns. However, the link between molecular and histologic features remains elusive. Here, we generated multiomics and spatially resolved molecular profiles of histologic patterns from primary lung adenocarcinoma, which we integrated with molecular data from >2,000 patients. The transition from indolent to aggressive patterns was not driven by genetic alterations but by epigenetic and transcriptional reprogramming reshaping cancer cell identity. A signature quantifying this transition was an independent predictor of patient prognosis in multiple human cohorts. Within individual tumors, highly multiplexed protein spatial profiling revealed coexistence of immune desert, inflamed, and excluded regions, which matched histologic pattern composition. Our results provide a detailed molecular map of lung adenocarcinoma intratumor spatial heterogeneity, tracing nongenetic routes of cancer evolution. SIGNIFICANCE: Lung adenocarcinomas are classified based on histologic pattern prevalence. However, individual tumors exhibit multiple patterns with unknown molecular features. We characterized nongenetic mechanisms underlying intratumor patterns and molecular markers predicting patient prognosis. Intratumor patterns determined diverse immune microenvironments, warranting their study in the context of current immunotherapies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据