Mei Li-Hong, Gan Hui-Hui, Wang Hong-Feng, Xu Guoxiong, Ye Xuan-Guang, Yang Gao
Department of Dermatology, Jinshan Hospital, Fudan University, Shanghai, China.
Department of Central Laboratory, Jinshan Hospital, Fudan University, Shanghai, China.
Front Mol Biosci. 2024 Jul 23;11:1356043. doi: 10.3389/fmolb.2024.1356043. eCollection 2024.
Skin squamous cell carcinoma (SCC) is a prevalent malignancy, and dysregulated lipid metabolism has been implicated in its pathogenesis. However, detailed characterization of lipid alterations in SCC remains limited.
We analyzed lipid metabolic variations in tissue samples from 34 SCC patients and adjacent healthy tissues (located more than 1 cm from the tumor margin) using liquid chromatography-mass spectrometry (LC-MS). Data visualization and discriminatory lipid profiles were identified using principal component analysis (PCA) and sparse partial least squares discriminant analysis (sPLS-DA). Key lipids involved in the SCC metabolism were identified and further validated using an external data set (from a previous study, which similarly explored lipid profiles in oral SCC using lipidomics approaches). Pathway enrichment analysis was conducted to elucidate the metabolic pathways associated with these key lipids.
Eight lipids were identified by comparing SCC and healthy tissues including PI(16:0/22:4), PI(18:1/20:4), PE(16:0/20:4), PE(16:0/22:5), PE(16:0/22:6), PE(18:1/20:3), PC(18:1/20:2), and PC(18:2/20:2), as confirmed by independent datasets. All of these lipids were upregulated in SCC tumor tissues. Pathway enrichment analysis revealed significant alterations in glycerophospholipid metabolic pathways, particularly affecting the metabolism of diacylglycerophosphocholines, glycerophosphoethanolamines, and glycerophosphoinositols.
Our findings reveal that dysregulated glycerophospholipid metabolism plays a pivotal role in the development of SCC.
皮肤鳞状细胞癌（SCC）是一种常见的恶性肿瘤，脂质代谢失调与其发病机制有关。然而，SCC中脂质改变的详细特征仍有限。
我们使用液相色谱 - 质谱联用（LC - MS）分析了34例SCC患者的组织样本和相邻健康组织（距肿瘤边缘超过1 cm）中的脂质代谢变化。使用主成分分析（PCA）和稀疏偏最小二乘判别分析（sPLS - DA）进行数据可视化和鉴别脂质谱分析。确定参与SCC代谢的关键脂质，并使用外部数据集（来自先前的一项研究，该研究同样使用脂质组学方法探索口腔SCC中的脂质谱）进行进一步验证。进行通路富集分析以阐明与这些关键脂质相关的代谢通路。
通过比较SCC和健康组织鉴定出8种脂质，包括PI(16:0/22:4)、PI(18:1/20:4)、PE(16:0/20:4)、PE(16:0/22:5)、PE(16:0/22:6)、PE(18:1/20:3)、PC(18:1/20:2)和PC(18:2/20:2)，独立数据集证实了这一点。所有这些脂质在SCC肿瘤组织中均上调。通路富集分析显示甘油磷脂代谢通路有显著改变，尤其影响二酰基甘油磷酸胆碱、甘油磷酸乙醇胺和甘油磷酸肌醇的代谢。
我们的研究结果表明，甘油磷脂代谢失调在SCC的发生发展中起关键作用。
