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).
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.
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.
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.
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We wish to acknowledge the Computational Biology Research Group, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine and University of Oxford for use of their services in this project. The facility is supported by the MRC Strategic Award to the institute. We also wish to acknowledge Drs. Koichi Tanaka and Taka-aki Sato at Shimadzu Corporation, and Techno-Research, Inc. for their crucial support in mass spectrometry analysis. We thank the support and advice from Toshifumi Fukui at the Medical Imaging System Development Center, Canon, and Professor Sigehira Saji at Fukushima Medical University for conducting the statistical analysis.
The authors declare no competing interests.
Ethics approval and consent to participate
Written informed consent was obtained from all patients prior to sample collection. The study protocol was approved by the Ethics Committee for Clinical Research, Kyoto University Hospital (authorisation number G424). This is also described in the “Methods” section.
This research was conducted under the support of the Ministry of Health, Labor and Welfare KAKENHI, the Ministry of Education, Culture, Sports, Science and Technology KAKENHI and the Japan Agency for Medical Research and Development. It was also supported by Cancer Research UK and the Breast Cancer Research Foundation.
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All data generated or analysed during this study are included in the supplementary tables. Alternatively, they are also available from the corresponding authors upon reasonable request.
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Kawashima, M., Tokiwa, M., Nishimura, T. et al. 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. Br J Cancer 122, 245–257 (2020). https://doi.org/10.1038/s41416-019-0662-8
British Journal of Cancer (2020)