Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavík, Iceland.
Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
PLoS One. 2020 Apr 14;15(4):e0231289. doi: 10.1371/journal.pone.0231289. eCollection 2020.
Breast cancer (BC) is the most prevalent type of cancer in women in western countries. BC mortality has not declined despite early detection by screening, indicating the need for better informed treatment decisions. Therefore, a novel noninvasive diagnostic tool for BC would give the opportunity of subtype-specific treatment and improved prospects for the patients. Heterogeneity of BC tumor subtypes is reflected in the expression levels of enzymes in lipid metabolism. The aim of the study was to investigate whether the subtype defined by the transcriptome is reflected in the lipidome of BC cell lines. A liquid chromatography mass spectrometry (LC-MS) platform was applied to analyze the lipidome of six cell lines derived from human BC cell lines representing different BC subtypes. We identified an increased abundance of triacylglycerols (TG) ≥ C-48 with moderate or multiple unsaturation in fatty acyl chains and down-regulated ether-phosphatidylethanolamines (PE) (C-34 to C-38) in cell lines representing estrogen receptor and progesterone receptor positive tumor subtypes. In a cell line representing HER2-overexpressing tumor subtype an elevated expression of TG (≤ C-46), phosphatidylcholines (PC) and PE containing short-chained (≤ C-16) saturated or monounsaturated fatty acids were observed. Increased abundance of PC ≥ C-40 was found in cell lines of triple negative BC subtype. In addition, differences were detected in lipidomes within these previously defined subtypes. We conclude that subtypes defined by the transcriptome are indeed reflected in differences in the lipidome and, furthermore, potentially biologically relevant differences may exist within these defined subtypes.
乳腺癌（BC）是西方国家女性中最常见的癌症类型。尽管通过筛查早期发现，但 BC 的死亡率并未下降，这表明需要做出更明智的治疗决策。因此，一种新型的非侵入性 BC 诊断工具将为患者提供特定亚型的治疗机会和改善前景。BC 肿瘤亚型的异质性反映在脂质代谢中酶的表达水平上。本研究旨在探讨转录组定义的亚型是否反映在 BC 细胞系的脂质组中。应用液相色谱-质谱（LC-MS）平台分析了代表不同 BC 亚型的 6 个人源 BC 细胞系衍生的细胞系的脂质组。我们发现，在代表雌激素受体和孕激素受体阳性肿瘤亚型的细胞系中，三酰基甘油（TG）≥C-48 的丰度增加，并且脂肪酸链中具有中度或多个不饱和性，醚磷脂酰乙醇胺（PE）（C-34 至 C-38）下调。在代表 HER2 过表达肿瘤亚型的细胞系中，观察到 TG（≤C-46）、含有短链（≤C-16）饱和或单不饱和脂肪酸的磷脂酰胆碱（PC）和 PE 的表达增加。在三阴性 BC 亚型的细胞系中发现 PC≥C-40 的丰度增加。此外，在这些先前定义的亚型内的脂质组中还检测到差异。我们得出结论，转录组定义的亚型确实反映在脂质组的差异中，此外，这些定义的亚型内可能存在潜在的生物学相关差异。
