Department of Thoracic Surgery, Kyoto city Hospital, Kyoto, Japan.
Department of General Thoracic Surgery, Breast and Pediatric Surgery, Fukuoka University School of Medicine, Fukuoka, Japan.
Sci Rep. 2019 Jun 20;9(1):8916. doi: 10.1038/s41598-019-45506-3.
Adenocarcinoma is the most common type of lung cancer, and can be classified into various histologic subtypes. However, little is known about the subtype-dependent variations in lipid metabolism processes. We performed dual lipidomic analyses using liquid chromatography-mass spectrometry (LC-MS) and matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to identify possible biomarkers to distinguish adenocarcinoma specimens from normal lung specimens, and to determine if there are any differences in lipid metabolism among the histologic subtypes (lepidic, acinar, papillary, micropapillary, solid, and mucinous). LC-MS was used to characterize the lipid profiles of lung adenocarcinoma and normal lung tissue, and MALDI-IMS analysis was performed to confirm the results with information on lipid localization within the lung. LC-MS analysis found significant differences in the relative abundances of phosphatidylcholine (PC)(16:0/16:0) (P = 0.0432) and sphingomyelin (SM)(42:2) (P < 0.0001) between adenocarcinoma and normal lung specimens. The ratios of PC(16:0/16:1)/PC(16:0/16:0), PC(16:0/18:1)/PC(16:0/16:0), and PC(16:0/18:1)/PC(16:0/18:0) were significantly higher in adenocarcinoma specimens (P = 0.02221, P = 0.0004, and P = 0.0215, respectively). MALDI-IMS analysis confirmed that these ratios were significantly higher in adenocarcinoma regions of the lung. The ratio of PC(16:0-18:1)/PC(16:0-18:0) was significantly lower in solid subtypes than in other subtypes (P = 0.0028). The monounsaturated/saturated PC ratios may have applications in adenocarcinoma diagnoses and subtyping.
腺癌是最常见的肺癌类型,可分为多种组织学亚型。然而,人们对脂质代谢过程中依赖于亚型的变化知之甚少。我们使用液相色谱-质谱联用 (LC-MS) 和基质辅助激光解吸/电离成像质谱 (MALDI-IMS) 进行双重脂质组学分析,以确定可能的生物标志物来区分腺癌标本和正常肺标本,并确定组织学亚型(贴壁型、腺泡型、乳头型、微乳头型、实体型和黏液型)之间的脂质代谢是否存在差异。LC-MS 用于描述肺腺癌和正常肺组织的脂质谱,MALDI-IMS 分析用于通过肺内脂质定位信息验证结果。LC-MS 分析发现腺癌和正常肺标本之间的磷脂酰胆碱 (PC)(16:0/16:0) (P = 0.0432) 和神经鞘磷脂 (SM)(42:2) (P < 0.0001) 的相对丰度存在显著差异。PC(16:0/16:1)/PC(16:0/16:0)、PC(16:0/18:1)/PC(16:0/16:0) 和 PC(16:0/18:1)/PC(16:0/18:0) 的比值在腺癌标本中明显更高(P = 0.02221,P = 0.0004 和 P = 0.0215)。MALDI-IMS 分析证实,这些比值在肺腺癌区域明显更高。在实体亚型中,PC(16:0-18:1)/PC(16:0-18:0) 的比值明显低于其他亚型(P = 0.0028)。单不饱和/饱和 PC 比值可能在腺癌诊断和亚型分类中有应用。