High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer

Masahiro Kawashima, Mariko Tokiwa, Tomomi Nishimura, Yukiko Kawata, Masahiro Sugimoto, Tatsuki R. Kataoka, Takaki Sakurai, Keiko Iwaisako, Eiji Suzuki, Masatoshi Hagiwara, Adrian L. Harris, Masakazu Toi

    Research output: Contribution to journalArticle

    1 Scopus citations

    Abstract

    Background: The fatty acid (FA) composition of phosphatidylinositols (PIs) is tightly regulated in mammalian tissue since its disruption impairs normal cellular functions. We previously found its significant alteration in breast cancer by using matrix-assisted laser desorption and ionisation imaging mass spectrometry (MALDI-IMS). Methods: We visualised the histological distribution of PIs containing different FAs in 65 primary breast cancer tissues using MALDI-IMS and investigated its association with clinicopathological features and gene expression profiles. Results: Normal ductal cells (n = 7) predominantly accumulated a PI containing polyunsaturated FA (PI-PUFA), PI(18:0/20:4). PI(18:0/20:4) was replaced by PIs containing monounsaturated FA (PIs-MUFA) in all non-invasive cancer cells (n = 12). While 54% of invasive cancer cells (n = 27) also accumulated PIs-MUFA, 46% of invasive cancer cells (n = 23) accumulated the PIs-PUFA, PI(18:0/20:3) and PI(18:0/20:4). The accumulation of PI(18:0/20:3) was associated with higher incidence of lymph node metastasis and activation of the PD-1-related immune checkpoint pathway. Fatty acid-binding protein 7 was identified as a putative molecule controlling PI composition. Conclusions: MALDI-IMS identified PI composition associated with invasion and nodal metastasis of breast cancer. The accumulation of PI(18:0/20:3) could affect the PD-1-related immune checkpoint pathway, although its precise mechanism should be further validated.

    Original languageEnglish (US)
    Pages (from-to)245-257
    Number of pages13
    JournalBritish journal of cancer
    Volume122
    Issue number2
    DOIs
    StatePublished - Jan 21 2020

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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