Lung cancer scRNA-seq and lipidomics reveal aberrant lipid metabolism for early-stage diagnosis

Sci Transl Med. 2022 Feb 2;14(630):eabk2756. doi: 10.1126/scitranslmed.abk2756. Epub 2022 Feb 2.

Abstract

Lung cancer is the leading cause of cancer mortality, and early detection is key to improving survival. However, there are no reliable blood-based tests currently available for early-stage lung cancer diagnosis. Here, we performed single-cell RNA sequencing of different early-stage lung cancers and found that lipid metabolism was broadly dysregulated in different cell types, with glycerophospholipid metabolism as the most altered lipid metabolism-related pathway. Untargeted lipidomics was carried out in an exploratory cohort of 311 participants. Through support vector machine algorithm-based and mass spectrum-based feature selection, we identified nine lipids (lysophosphatidylcholines 16:0, 18:0, and 20:4; phosphatidylcholines 16:0-18:1, 16:0-18:2, 18:0-18:1, 18:0-18:2, and 16:0-22:6; and triglycerides 16:0-18:1-18:1) as the features most important for early-stage cancer detection. Using these nine features, we developed a liquid chromatography-mass spectrometry (MS)-based targeted assay using multiple reaction monitoring. This target assay achieved 100.00% specificity on an independent validation cohort. In a hospital-based lung cancer screening cohort of 1036 participants examined by low-dose computed tomography and a prospective clinical cohort containing 109 participants, the assay reached more than 90.00% sensitivity and 92.00% specificity. Accordingly, matrix-assisted laser desorption/ionization MS imaging confirmed that the selected lipids were differentially expressed in early-stage lung cancer tissues in situ. This method, designated as Lung Cancer Artificial Intelligence Detector, may be useful for early detection of lung cancer or large-scale screening of high-risk populations for cancer prevention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artificial Intelligence
  • Early Detection of Cancer
  • Humans
  • Lipid Metabolism / genetics
  • Lipidomics*
  • Lipids / analysis
  • Lung Neoplasms* / diagnosis
  • Prospective Studies
  • Single-Cell Analysis
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Lipids