High-dimensionality reduction clustering of complex carbohydrates to study lung cancer metabolic heterogeneity.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0370416 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2162-5557 (Electronic) Linking ISSN: 0065230X NLM ISO Abbreviation: Adv Cancer Res Subsets: MEDLINE
    • Publication Information:
      Publication: <2008>- : Amsterdam : Elsevier
      Original Publication: New York : Academic Press
    • Subject Terms:
      Lung Neoplasms*; Cluster Analysis ; Humans ; Polysaccharides ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Tumor Microenvironment
    • Abstract:
      The tumor microenvironment contains a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression. Due to heterogeneity within solid tumors, pooled mass spectrometry workflows are less sensitive at delineating unique metabolic perturbations between stromal and immune cell populations. Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. Together, these complex carbohydrates modulate bioenergetics and protein-structure function, and create functional microanatomy in distinct cell populations within the tumor heterogeneity. Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. In-depth pathway enrichment analyses revealed unique metabolic pathways are associated with each distinct pathological region. Further, we highlight the potential of HDRC analysis to study complex carbohydrate metabolism in a case study of lung cancer disparity. Collectively, our results demonstrate the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment.
      (Copyright © 2022 Elsevier Inc. All rights reserved.)
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    • Grant Information:
      R01 AG066653 United States AG NIA NIH HHS; R25 CA221765 United States CA NCI NIH HHS; R35 NS116824 United States NS NINDS NIH HHS; T32 CA165990 United States CA NCI NIH HHS; P30 CA177558 United States CA NCI NIH HHS
    • Contributed Indexing:
      Keywords: Clustering analysis; Glycogen; Lung cancer; MALDI imaging; N-linked glycans
    • Accession Number:
      0 (Polysaccharides)
    • Publication Date:
      Date Created: 20220423 Date Completed: 20220426 Latest Revision: 20230319
    • Publication Date:
      20240105
    • Accession Number:
      PMC9273336
    • Accession Number:
      10.1016/bs.acr.2022.02.005
    • Accession Number:
      35459471