Evolutionary metabolic landscape from preneoplasia to invasive lung adenocarcinoma

Meng Nie, Ke Yao, Xinsheng Zhu, Na Chen, Nan Xiao, Yi Wang, Bo Peng, LiAng Yao, Peng Li, Peng Zhang () and Zeping Hu ()
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Meng Nie: Tsinghua University
Ke Yao: Tsinghua University
Xinsheng Zhu: Tongji University School of Medicine
Na Chen: Tsinghua University
Nan Xiao: Tsinghua University
Yi Wang: Tsinghua University
Bo Peng: Tsinghua University
LiAng Yao: Tsinghua University
Peng Li: Fudan University
Peng Zhang: Tongji University School of Medicine
Zeping Hu: Tsinghua University

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Metabolic reprogramming evolves during cancer initiation and progression. However, thorough understanding of metabolic evolution from preneoplasia to lung adenocarcinoma (LUAD) is still limited. Here, we perform large-scale targeted metabolomics on resected lesions and plasma obtained from invasive LUAD and its precursors, and decipher the metabolic trajectories from atypical adenomatous hyperplasia (AAH) to adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC), revealing that perturbed metabolic pathways emerge early in premalignant lesions. Furthermore, three panels of plasma metabolites are identified as non-invasive predictive biomarkers to distinguish IAC and its precursors with benign diseases. Strikingly, metabolomics clustering defines three metabolic subtypes of IAC patients with distinct clinical characteristics. We identify correlation between aberrant bile acid metabolism in subtype III with poor clinical features and demonstrate dysregulated bile acid metabolism promotes migration of LUAD, which could be exploited as potential targetable vulnerability and for stratifying patients. Collectively, the comprehensive landscape of the metabolic evolution along the development of LUAD will improve early detection and provide impactful therapeutic strategies.

Date: 2021
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DOI: 10.1038/s41467-021-26685-y

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