Short communication: Distribution of phospholipids in parotid cancer by matrix-assisted laser desorption/ionization imaging mass spectrometry

Abstract

Background Parotid cancer is relatively rare, and malignancy varies; therefore, novel markers are needed to predict prognosis. Recent advances in matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), useful for visualization of lipid molecules, have revealed the relationship between cancer and lipid metabolism, indicating the potential of lipids as biomarkers. However, the distribution and importance of phospholipids in parotid cancer remain unclear. Objective This study aimed to use MALDI-IMS to comprehensively investigate the spatial distribution of phospholipids characteristically expressed in human parotid cancer tissues. Methods Tissue samples were surgically collected from two patients with parotid cancer (acinic cell carcinoma and mucoepidermoid carcinoma). Frozen sections of the samples were assessed using MALDI-IMS in both positive and negative ion modes, with an m/z range of 600–1000. The mass spectra obtained in the tumor and non-tumor regions were compared and analyzed. Ion images corresponding to the peak characteristics of the tumor regions were visualized. Results Several candidate phospholipids with significantly different expression levels were detected between the tumor and non-tumor regions. The number of unique lipid peaks with significantly different intensities between the tumor and non-tumor regions was 95 and 85 for Cases 1 and 2, respectively, in positive ion mode, and 99 and 97 for Cases 1 and 2, respectively, in negative ion mode. Imaging differentiated the characteristics that phospholipids were heterogeneously distributed in the tumor regions. Conclusion Phospholipid candidates that are characteristically expressed in human parotid cancer tissues were found, demonstrating the localization of their expression. These findings are notable for further investigation of alterations in lipid metabolism of parotid cancer and may have potential for the development of phospholipids as biomarkers.

MALDI Mass Spectrometry Imaging Highlights Specific Metabolome and Lipidome Profiles in Salivary Gland Tumor Tissues

“…Conversely, the distribution patterns of PC 34:2, PC O-38:4, and PE O-38:6 were reduced in the parotid tumor regions, in accordance with a previous MALDI-MSI lipidomic analysis in the same cancerous model of two patient-derived biopsies [19].…”

“…Interestingly, the dysregulations of several sphingomyelins (SMs) and triacylglycerols (TGs) were observed, which have never (or poorly) been investigated for other forms of oral and neck tumors [17,19,36].…”

“…The complex lipid metabolic changes may be explained by the high proliferation rate of cancerous cells leading to continuous cell membrane synthesis, disruption of energy homeostasis, sustained cell signaling, and protein distribution, with variations in the serum or tissue levels of phospholipid components [18]. In this regard, previous MALDI imaging data have highlighted global lipidomic changes associated with head and neck cancer tissues [17,19]. In particular, phosphatidylcholine distribution (visualized through MSI) has specifically increased in the Warthin tumor lymphoid stroma of salivary glands [20].…”