Characterization of metabolic landscape in hepatocellular carcinoma

Table 1 Summary of metabolism-based diagnostic tools or markers and treatment agents

	Markers, tools, or agents	Functions	Ref.
Diagnosis	18F-FDG PET/CT	Monitor non-invasively the development of HCC; studied as predictors of overall survival and tumor recurrence after related treatments in HCC	Hwang et al[41], 2017
			Levy et al[40], 2019
			Lim et al[42], 2019
	C-11 acetate PET/CT	Detect glycolysis-independent HCC and metastatic sites	Yoo et al[43], 2021
			Lee et al[44], 2018
	[18F]FSPG PET/CT	Entail a higher detection rate of HCC than 18F-FDG; the accumulation of [18F]FSPG is significantly lower than that of 18F-FDG in heathy liver	Baek et al[46], 2013
	Acetyl-carnitine	Serving as a marker for monitoring the development of HCC, with a supplementary role to AFP	Lu et al[48], 2016
	Serum AEA and PEA	AEA, PEA, or their combination show better sensitivity and specificity in distinguishing HCC infected with HBV or HCV from chronic liver diseases	Zhou et al[50], 2012
	10 metabolites identified by multivariate analysis: Butanoic acid, ethanimidic acid, glycerol, L-isoleucine, L-valine, aminomalonic acid, D-erythrose, hexadecanoic acid, octadecanoic acid, 9, 12-octadecadienoic acid	A diagnostic model built on a combination of these metabolites could well discriminate HCC patients from normal subjects	Xue et al[51], 2008
	11 metabolites identified by LASSO regression: Valine, serine, glycine, isoleucine, creatinine, pyroglutamic acid/glutamic acid, furanose sugar, linoleic acid, alpha-D-glucosamine 1-phospate, phosphoric acid, lauric acid	Diagnostic model constructed using this panel of 11 metabolites in conjunction with three clinical variates including AFP, Child–Pugh score, and etiologic factors achieves a higher accuracy in distinguishing HCC from liver cirrhosis	Di Poto et al[52], 2017
	13 metabolites identified by partial least-squares-latent structure discriminate analysis	These metabolic profiles were capable of discriminating not only patients from the controls but also HCC from liver cirrhosis with 100% sensitivity and specificity	Wang et al[54], 2012
Treatment	2-deoxy-D-glucose	Hinder tumor progression through inducing apoptosis; reverse sorafenib resistance	Lin et al[57], 2020
			Wong et al[56], 2020
	3-BP	3-BP is another antiglycolytic agent that functions via directly restraining HK2; 3-BP was lethal to both primary liver tumor and metastatic tumors arising from the lungs, but without any toxic side effects; 3-BP can induce apoptosis and destruct cellular antioxidative defense	Ganapathy-Kanniappan et al[59], 2010
			Ko et al[58], 2001
	Metformin	Metformin can inhibit complex I and result in ATP reduction, which further activates AMPK. Metformin participates in various anti-tumor action-related processes including inflammatory response, insulin regulation, immune response, mTORC1 activation, and folate metabolism	Hu et al[13], 2019
			Podhorecka et al[60], 2017
	TVB-2640	Serving as an inhibitor of FASN, which has a metabolo-oncogenic nature	Menendez and Lupu[62], 2017

3-BP: 3-bromopyruvate; ATP: Adenosine triphosphate; FASN: Fatty acid synthase; AMPK: Activated protein kinase; HCC: Hepatocellular carcinoma; AFP: Alpha-fetoprotein; AEA: Arachidonylethanolamine; PEA: Palmitoylethanolamide; HCV: Hepatitis C virus; 18F-FDG PET/CT: F-18 fluorodeoxyglucose positron emission tomography/computed tomography.