Targeting Strategies for Aberrant Lipid Metabolism Reprogramming and the Immune Microenvironment in Esophageal Cancer: A Review

Table 1

Cancer cell biomarkers for prognosis of esophageal cancer.

Markers	Cancer Type EAC/ESCC	Significance	Name	Marker for diagnosis or prognosis	Reference
ACSS2	ESCC	ACSS2 can recycle acetate (including both protein and metabolite deacetylation reactions) to produce acetyl-CoA, which is a raw material for fatty acid and cholesterol synthesis [36].	Lei et al.	The expression of ACSS2 is closely related to the prognosis of patients with ESCC.	[37]
ACC	ESCC	Acetyl-CoA carboxylase catalyzes the conversion of acetyl-CoA to malonyl-CoA. ACC promotes FA synthesis and the energy metabolism.	Zhao et al.	Downregulation the expression of p-ACC is associated with tumor cell differentiation in ESCC.	[50]
FASN	ESCC	FASN is a key enzyme for lipid metabolism and is associated with tumor invasion and metastasis [38].	Ishimura et al.	FASN expression was associated with the risk of malignancy progression.	[39]
	Barrett’s esophagus/OAC		Wang et al.	FASN promotes the development of esophageal squamous cell carcinoma.	[40]
	ESCC/OAC		Zhou et al.	FAS has the potential to be oncogenic in EC.	[41]
SCD1	ESCC	SCD1 appears to be a significant player in the development of tumor and may be a promising target for anticancer therapy [51].	Zemanova et al.	Compared with healthy patients, both saturated and monounsaturated fatty acids were increased in esophageal cancer patients due to increased activity of SCD1	[52]
ELOVL5		ELOVL5 is a key enzyme for de novo synthesis of long-chain unsaturated fatty acids.	Zhao et al.	ELOVL5 is upregulated in EC and is associated with a poor prognosis in patients.	[53]
CD36	ESCC	CD36-driven lipid metabolic reprogramming and tumor development [54].	Yoshida et al.	CD36 was associated with tumor invasion and metastasis in ESCC.	[31]
			Wang et al.	Overexpression of SREBP1 was significantly correlated with tumor differentiation and lymph node metastasis of ESCC.	[34]
SREBP1	ESCC	SREBP1 may provide the potential for the diagnosis and treatment of ESCC.	Shao et al.	SREBP1 can be used as an independent prognostic marker for ESCC.	[55]
		SREBP1 exerts oncogenic effects in ESCC by promoting proliferation and inducing epithelial-mesenchymal transition via the SCD1-induced activation of the Wnt/β-catenin signaling pathway.	Wang et al.	SREBP1 contributes to the development of novel biomarkers and therapeutic targets for ESCC.	[34]
SREBP2	ESCC	Sterol regulatory element-binding protein 2 (SREBP2), the master regulator for HMGCR, is upregulated in ESCC clinical samples.	Zhong et al.	SREBP2 is closely related to ESCC tumorigenesis.	[42]
CPT1A	ESCC	CPT1A acts as a key enzyme in fatty acid oxidation and regulates tumor energy metabolism.	Shi et al.	CPT1A is capable of potential biomarkers for the risk prediction for ESCC.	[46]
Carnitine		Levels of octanoylcarnitine, lysoPC (16 : 1), and decanoylcarnitine are closely related to the effectiveness of ESCC treatment [44, 56].	Li et al.	Carnitine is capable of potential biomarker for the risk prediction and early detection of ESCC.	[57]
l-Carnitine/acylcarnitin	ESCC		Xu et al.	Acylcarnitine is a potential biomarker of ESCC	[58]
Octanoylcarnitine, lysoPC (16 : 1), and decanoylcarnitine	ESCC	Levels of octanoylcarnitine, lysoPC (16 : 1), and decanoylcarnitine have been reported to be associated with the treatment effects and are identified as potential biomarkers.	Xu et al.	Levels of octanoylcarnitine, lysoPC (16 : 1), and decanoylcarnitine have been reported to be associated with the treatment effects and are identified as potential biomarkers.	[59]
LDs	Barrett’s esophagus/OAC	Lipid droplets are dynamically active and control lipid homeostasis.	Carrossini et al.	LDs are increased along EAC evolution as a consequence of the exposure of the esophageal epithelium to the risk factors associated with BE and EAC.	[49]
Cholesterol	ESCC/OAC	Cholesterol is a useful component of lipid rafts and controls various signaling pathway.	Zhu et al.	Cholesterol can be used as a potential biomarker of EC.	[43]
LPCAT1	ESCC	LPCAT1 regulates SREBP1 and SREBP2-related signaling pathways in ESCC cells.	Tao et al.	LPCAT1 may be a useful biomarker for ESCC diagnosis and prognosis.	[60]
HMGCR	ESCC	3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is the rate-limiting enzyme in cholesterol biosynthesis.	Zhong et al.	HMGCR may be an important therapeutic target for esophageal squamous cell carcinoma.	[35]
FABP1	OAC	Fatty acid-binding proteins (FABPs) are intracellular proteins that bind long-chain fatty acids (FA) and are related to immunometabolic diseases.	Srivastava et al.	FABP1 can clearly discriminate Barrett’s esophagus from columnar lined esophagus.	[48]
HNRNPA2B1	ESCC/EAC (both)	HNRNPA2B1 upregulates ACLY and ACC1 and promotes ESCA progression.	Guo et al.	HNRNPA2B1 can be a useful ESCA prognostic biomarker and therapeutic target.	[61]
Long-chain fatty acids	ESCC	De novo synthesis of strong fatty acids during esophageal cancer cell proliferation and metastasis leads to increased serum long-chain fatty acids.	Jin et al.	Long-chain fatty acids are used as a metabolic sign of tumorigenesis and metastasis of ESCC.	[45]
Linoleic acid	ESCC	Linoleic acid as a metabolite marker	Zhang et al.	Linoleic acid is used to discriminate ESCC and ESD patients and provides helpful reference for clinicians.	[62]
Phosphatidylcholines and choline kinase	ESCC	The key enzyme in the phosphatidylcholine metabolism pathway	Ma et al.	Phosphatidylcholines may be used as novel biomarkers for ESCC.	[63]
PGE2	ESCC	Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates different stages of the immune response.	Kuo et al.	EP2 expression became an independent factor of overall survival. EP2 overexpression is associated with worse prognosis and correlated positively with T status in ESCC.	[64]
LPE and LPC	Esophageal squamous dysplasia (ESD)/ESCC	Lysophosphatidylethanolamine (LPE) and lysophosphatidylcholine (LPC) serve as a new panel of plasma biomarkers to predict ESCC development.	Zhu et al.	LPE and LPC demonstrated a good diagnostic value.	[8]
FADS1	ESCC	Fatty acid desaturase 1 (FADS1), the rate-limiting enzyme, participates in the desaturation and elongation cascade of polyunsaturated fatty acids to generate long-chain PUFAs.	Du et al.	FADS1 might be a valuable biomarker and potential therapeutic target for ESCC.	[65]
Palmitoleic acid palmitaldehyde isobutyl decanoate	ESCC	A marker board consisting of palmitoleic acid, palmitaldehyde, and isobutyl caprate may be used as an innovative biomarker for the diagnosis and prognosis of ESCC.	Zhu et al.	Palmitoleic acid, palmitaldehyde, and isobutyl decanoate are used as diagnostic biomarkers of ESCC patients.	[47]
Apolipoprotein A1	ESCC	A major component of HDL.	Wang et al.	Apolipoprotein A1 is associated with ESCC patient survival rate.	[66]
CRABP2	ESCC	The CRABP2 gene, a member of the retinoic acid-binding protein family, binds to retinoic acid in the cytoplasm, transports it, and activates the transcription of related genes.	Li et al.	CRABP2 as a suppressor factor is associated with ESCC prognosis.	[67]