Lipid metabolism-related genes in gastric cancer: Exploring oncogenic pathways

Table 1 Overview of lipid metabolism-associated genes in gastric cancer

Gene	Description	Evidence	Importance
FASN	Enzyme essential for FASN, membrane integrity, and cell proliferation	Higher expression in GC tissues than normal tissues, associated with metastasis, lymphatic spread, and poor prognosis in GC	Prognosis treatment
ACC	Cytosolic enzyme that generates acetyl-CoA from citrate	ACC expression is increased in GC tissues. Increased expression of pACC in GC tissues is related to good prognosis of GC	Prognosis treatment
ACSS	In fatty acid metabolism it converts acetyl-CoA to malonyl-CoA for long-chain fatty acid	Expression of ACSS3 is increased and that of ACSS2 is decreased in GCs. Low expression of ACSS2 is related to poor prognosis	Cancer progression prognosis
FABP	Binds long-chain fatty acids and other lipids, performing diverse functions	FABP5 is related to increased proliferation of GC. FABP4 and H-FABP are associated with poor prognosis in GIST and GCs respectively	Cancer progression prognosis treatment
SCD1	Endoplasmic reticulum membrane enzyme that converts saturated fatty acids into monounsaturated fatty acids	Increased expression of SCD1 is related to increased proliferation and metastasis of GC	Cancer progression prognosis treatment
LPL	Hydrolyze triglycerides in chylomicrons and VLDL in the bloodstream	Rs15285 genotype is associated with increased risk of GC, poor prognosis and increased malignancy of GC	Cancer risk progression prognosis
SREBPs	Transcription factors regulating genes for fatty acid and cholesterol biosynthesis, essential for cell proliferation and survival	SREBPs are involved in lymph node metastasis of GC	Cancer progression treatment
ACLY	Converts acetate to acetyl-CoA, crucial for fatty acid and cholesterol biosynthesis	Increased expression of ACLY is associated with lymph node and peritoneal metastasis of GC and is a marker of poor prognosis	Cancer progression prognosis treatment
CPT1	Transports long-chain fatty acids into mitochondria for β-oxidation and regulating fatty acid oxidation	Overexpression of CPT1 is associated with increased cell proliferation, metastasis and poor prognosis of GC	Cancer progression prognosis treatment
LXRs	Nuclear receptors (LXRα/NR1H3 and LXRβ/NR1H2) crucial in metabolic pathways and cellular processes	Overexpression of LXRα has been implicated in promoting invasion and epithelial-mesenchymal transition of GC cells

ACC: Acetyl-CoA carboxylase; ACLY: ATP citrate lyase; ACSS: Acetyl-CoA synthetase; CPT1: Carnitine palmitoyltransferase 1; FABP: Fatty acid binding protein; FASN: Fatty acid synthase; GC: Gastric cancer; H-FABP: Heart-type fatty acid binding protein; LXRs: Liver X receptors; pACC: Phosphorylated acetyl-CoA carboxylase; GIST: Gastrointestinal stromal tumor; LPL: Lipoprotein lipase; SCD1: Stearoyl-CoA desaturase 1; SREBPs: Sterol regulatory element-binding proteins; VLDL: Very low-density lipoprotein.

Table 2 Technologies employed to study the role of lipid metabolism-associated genes in gastric cancer

Technology	Description	Uses and importance in GC
Mass spectrometry	Analytical technique identifying molecules based on their mass-to-charge ratio. It provides quantitative and qualitative analysis of compounds in a sample	Detects biomarkers and metabolic alterations in GC tissues. Characterizing the metabolic profile of GC cells for personalized treatment strategies
Single-cell RNA sequencing	Molecular biology technique enabling transcriptomic analysis of individual cells, revealing gene expression patterns and cellular heterogeneity	Identifies distinct cell populations within gastric tumors, aiding in understanding tumor heterogeneity. Uncovering gene expression changes associated with cancer progression and metastasis
The Cancer Genome Atlas	Comprehensive database containing genomic, transcriptomic, and clinical data from various cancers, including GC	Provides insights into genetic alterations, molecular subtypes, and pathways involved in GC development. Facilitating the discovery of potential therapeutic targets and biomarkers for diagnosis and prognosis

GC: Gastric cancer.

Table 3 Inhibitors of lipogenic enzymes involved in gastric cancer

Inhibitor	Target	Comment	Ref.
Berberine	FABPs	Trigger cell apoptosis by regulating fatty acid metabolism	[57]
Omeprazole	ACLY	Suppress de novo lipogenesis in gastric epithelial cells	[58]
Orlistat	FASN	Increase survival from GC	[59]
A939572	SCD1	Disrupts lipid homeostasis	[60]
Perihexiline	CPT1	Its combination with oxaliptin suppress progression of GIT cancer	[61]
Avasimbe	ACAT1	Target the metabolism of cholesterol of primary gastric tumors	[62]

ACAT1: Acetyl coenzyme A acetyltransferase; ACLY: ATP-citrate lyase; CPT1: Carnitine palmitoyltransferase 1; FABPs: Fatty acid binding proteins; FASN: Fatty acid synthase; GC: Gastric cancer; GIT: Gastrointestinal tract 1; SCD1: Stearoyl-CoA desaturase 1.