TABLE 1

List of differentially expressed DMEs during carcinogenesis and their functions

Cancer typeVariation TrendFunctional ClassificationDMEsRoles in CancerReference
Liver cancerUpregulationIncreased activation of procarcinogensCYP1B1CYP1B1 increases the HCC risk and associated with the activation of procarcinogens.Su et al., 2007; Liu et al., 2015
DownregulationPotential impact on drug efficacy and toxicityCYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5They are responsible for the metabolism of various drugs. Because of the decrease of functional hepatocytes, their expressions are downregulated, which may reduce drug efficacy and increase drug toxicity.Chen et al., 2014; Yan et al., 2015a; Hu et al., 2019
Potential biomarkers in cancerCYP2E1CYP2E1 activity decreases during hepatocarcinogenesis, the specific mechanism remains unknown.Ho et al., 2004
CYP11A1The loss of CYP11A1 contributes to abnormal steroid synthesis.Fan et al., 2016
Decreased inactivation of carcinogensCYP26A1CYP26A1 participates in the inactivation of retinoic acid, which may promote HCC progression.Brodeur et al., 2019
NAT1, NAT2They are responsible for the biotransformation of most arylamine and hydrazine substrates.Yu et al., 2000; Hu et al., 2019
UGT1A1, UGT1A4, UGT1A9, UGT2B7These UGTs detoxify endogenous and environmental carcinogens through glucuronidation reaction.Lu et al., 2015; Yan et al., 2015b
GSTP1GSTP1 is a detoxifying enzyme that protects cells from various stimuli such as hypoxia and oxidative stress.Tchou et al., 2000; Li et al., 2018
Lung cancerUpregulationCatabolism of antiproliferation compoundCYP24A1CYP24A1 catabolizes the antiproliferation compound 1, 25-D3.Chen et al., 2011b
Increased activation of procarcinogensCYP1A1, CYP1B1They catalyze the activation of carcinogens related to tobacco use, such as NNK and PAHs.Li et al., 2015b; Zhang et al., 2019
CYP19A1CYP19A1 is an estrogen synthesis enzyme that can promote the steroidal growth-stimulatory pathway.Weinberg et al., 2005
DownregulationPotential biomarkers in cancerADH1BADH1B is indispensable in the metabolism of fatty acids, retinoid, and ethanol, which are associated with lung cancer.Mutka et al., 2012
CYP3A7, CYP4B1The specific role is not clear.Leclerc et al., 2011
CYP11A1The loss of CYP11A1 contributes to abnormal steroid synthesis.Fan et al., 2016
Decreased inactivation of carcinogensGST-M2GST-M2 is a detoxifying enzyme that can protect lung cells from DNA damage.Tang et al., 2011
Prostate cancerUpregulationIncreased activation of procarcinogensCYP1A1CYP1A1 mediates the metabolic activation of procarcinogens PAHs.Mitsui et al., 2016
Elimination of anticancer drugsCYP1B1CYP1B1 metabolizes estradiol to carcinogen 4-hydroxy estradiol and is related to the resistance to docetaxel.Pastina et al., 2010
Potential biomarkers in cancerUGT2B17UGT2B17 is responsible for the elimination of the inactive metabolites androstane-3α-diol and androsterone. It is also associated with metastasis.Pâquet et al., 2012; Lévesque et al., 2020
DownregulationDecreased inactivation of carcinogensCYP3A4, CYP2B6They are key inactivators of testosterone which are significantly related to the development of prostate cancer.Kumagai et al., 2007; Fujimura et al., 2009
GSTP1The loss of GSTP1 leads to an increase of intracellular reactive oxygen species (ROS) and DNA damage; promotes the occurrence of cancer.Hokaiwado et al., 2008; Kanwal et al., 2014
UGT2B15UGT2B15 is a negatively regulated target gene in castration-resistant prostate cancer (CRPC), inactivating the active androgen dihydrotestosterone in prostate cells.Pâquet et al., 2012
Potential biomarkers in cancerCYP11A1The loss of CYP11A1 contributes to abnormal steroid synthesis.Fan et al., 2016
Breast cancerUpregulationIncreased activation of procarcinogensCYP1B1CYP1B1 metabolizes estradiol to carcinogen 4-hydroxy estradiol, resulting in DNA adducts.Gajjar et al., 2012
Promote tumor growthCYP4Z1CYP4Z1 is a fatty acid hydroxylase that promotes angiogenesis and the development of breast cancer.Yu et al., 2012
DownregulationDecreased inactivation of carcinogensGSTP1GSTP1 detoxifies carcinogens and cytotoxic drugs.Schnekenburger et al., 2014
Kidney cancerDownregulationPotential impact on drug efficacy and toxicityUGT1A9, UGT2B7UGT1A9 and UGT2B7 are responsible for the clearance of drugs such as propofol and sorafenib in the kidney.Margaillan et al., 2015
Esophageal cancerUpregulationPromote tumor growthCYP2C9CYP2C9 promotes the proliferation of early esophageal cancer.Schmelzle et al., 2011
Ovarian cancerUpregulationIncreased activation of procarcinogensCYP1B1CYP1B1 metabolizes estradiol to carcinogen 4-hydroxy estradiol.Gajjar et al., 2012
Elimination of anticancer drugsGSTP1GSTP1 is closely related to the chemoresistance of platinum drugs.Sawers et al., 2014
Colorectal cancerUpregulationIncreased activation of procarcinogensCYP1A1CYP1A1 participates in the metabolic activation of PAHs in tobacco and increases the risk of colorectal cancer.Slattery et al., 2004
CYP2E1CYP2E1 is involved in the metabolic activation of potent carcinogens azoxymethane and methylazoxymethanol.Sohn et al., 2001
Bladder cancerUpregulationIncreased activation of procarcinogensCYP4B1CYP4B1 metabolic activates the carcinogen 2-aminofluorene.Imaoka et al., 2000
DownregulationPotential biomarkers in cancerCYP1A1, CYP1B1Metabolomic profiling revealed their deficiency in bladder cancer; the specific mechanism remains unknown.Putluri et al., 2011
Hematologic malignancyUpregulationIncreased activation of procarcinogensCYP2J2CYP2J2 converts arachidonic acid to carcinogen epoxyeicosatrienoic acids and promotes cancer growth.Chen et al., 2011a