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

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 C20:0, 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 d18:1/12:0
and Cer d16:1/14:0, Cer d18:0/16:0, Cer d18:1/16:0, Cer d18:2/16:0,
Cer d18:2/18:0), short–medium-chain (C2–C16) acylcarnitines,
LPC 20:0 and LPC 22:1, and significantly increased levels of the long-chain
acylcarnitine C20:0, LPC 16:0, LPC P-16:0, LPC 20:1, LPC 20:2, glyceroPC,
LPE 16:0, and LPE 18:2. In squamous cell carcinoma (SCC) tissues,
sphingosine, Cer d18:2/16:0 and Cer d18:2/18:0, and short–medium-chain
acylcarnitines had significantly lower levels, while long-chain acylcarnitines
(C20:0, and C22:0 or C22:0 M), LPC 20:1, LPC 20:2, and N1,N12-diacetylspermine
had significantly higher levels compared to controls. In AC and SCC
tissues, the levels of LPG 18:0, LPG 18:1, and LPS 18:1 were significantly
decreased, while the levels of ceramide-1-phosphate (C1P) d18:0/3:0
or LPE P-16:0, 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.