Alterations of Ceramides, Acylcarnitines, GlyceroLPLs, and Amines in NSCLC Tissues.

ABSTRACT

Abnormal lipid metabolism plays an important role in cancer development. In this study, nontargeted lipidomic study on 230 tissue specimens from 79 nonsmall cell lung cancer (NSCLC) patients was conducted using ultraperformance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Downregulation of sphingosine and medium-long-chain ceramides and short-medium-chain acylcarnitine, upregulation of long-chain acylcarnitine C200, and enhanced histamine methylation were revealed in NSCLC tissues. Compared with paired noncancerous tissues, adenocarcinoma (AC) tissues had significantly decreased levels of sphingosine, medium-long-chain ceramides (Cer d181/120 and Cer d161/140, Cer d180/160, Cer d181/160, Cer d182/160, Cer d182/180), short-medium-chain (C2-C16) acylcarnitines, LPC 200 and LPC 221, and significantly increased levels of the long-chain acylcarnitine C200, LPC 160, LPC P-160, LPC 201, LPC 202, glyceroPC, LPE 160, and LPE 182. In squamous cell carcinoma (SCC) tissues, sphingosine, Cer d182/160 and Cer d182/180, and short-medium-chain acylcarnitines had significantly lower levels, while long-chain acylcarnitines (C200, and C220 or C220 M), LPC 201, LPC 202, and N1,N12-diacetylspermine had significantly higher levels compared to controls. In AC and SCC tissues, the levels of LPG 180, LPG 181, and LPS 181 were significantly decreased, while the levels of ceramide-1-phosphate (C1P) d180/30 or LPE P-160, N1-acetylspermidine, and 1-methylhistamine were significantly increased than controls. Furthermore, an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model based on a 4-lipid panel was established, showing good discrimination ability between cancerous and noncancerous tissues.