Table 4.
Consistently Down-Regulated Genes Associated With Hepatocyte Metabolic Functions Correlate With Expression of Progression Markers and Predict Survival Outcome in HCC Patients
| Metabolic process | Gene symbol | # of datasets | Expression | Correlationa |
Predicts overall survivalb | |
|---|---|---|---|---|---|---|
| CDH1 | VIM | |||||
| Xenobiotics | CYP4A11 | 7 | Down | c | .0001 | |
| CYP4F3 | 8 | Down | c | c | .0007 | |
| CYP3A4 | 7 | Down | c | .001 | ||
| CYP2J2 | 7 | Down | c | .0012 | ||
| ▪HSD17B6 | 8 | Down | c | .0018 | ||
| CYP2C8 | 8 | Down | c | .0022 | ||
| ▪SRD5A1 | 7 | Down | c | .0038 | ||
| CYP2A6 | 7 | Down | c | .0051 | ||
| HSD11B1 | 7 | Down | c | .0307 | ||
| CYP2A7 | 6 | Down | .0346 | |||
| CYP3A43 | 7 | Down | c | <.0001 | ||
| Detoxification | ▪FMO4 | 6 | Down | c | .0011 | |
| ▪EPHX2 | 7 | Down | c | c | .0032 | |
| ▪TPMT | 8 | Down | c | .0032 | ||
| CAT | 7 | Down | c | .0053 | ||
| FMO3 | 6 | Down | c | .0065 | ||
| Urea cycle | OTC | 7 | Down | c | .0055 | |
| ASL | 6 | Down | c | c | .0074 | |
| CPS1 | 7 | Down | c | .011 | ||
| Redox | ▪FDX1 | 7 | Down | c | .0081 | |
| ▪DHRS12 | 6 | Down | c | .0141 | ||
| ▪DHTKD1 | 6 | Down | c | .0167 | ||
| ▪DHRS1 | 7 | Down | c | <.0001 | ||
| CYB5A | 8 | Down | c | .0026 | ||
| Glutathione | ▪HAGH | 7 | Down | c | .0015 | |
| ▪MGST2 | 6 | Down | c | .0493 | ||
| Fatty acid | ACOX2 | 7 | Down | c | .0003 | |
| ▪ECHDC2 | 8 | Down | c | .0004 | ||
| ▪ACADM | 7 | Down | c | .0007 | ||
| ▪ACBD4 | 8 | Down | c | .0012 | ||
| ▪FAAH | 6 | Down | c | .0015 | ||
| ▪ACAA2 | 7 | Down | c | .0018 | ||
| ▪ACSM3 | 7 | Down | c | .002 | ||
| ▪PECR | 6 | Down | c | .0022 | ||
| ▪ETFDH | 8 | Down | c | .0028 | ||
| ▪ACSM5 | 7 | Down | c | .0104 | ||
| EHHADH | 7 | Down | c | .0115 | ||
| ACADVL | 6 | Down | .0127 | |||
| MTTP | 6 | Down | c | .0134 | ||
| ▪ACADSB | 8 | Down | c | .0212 | ||
| ▪SCP2 | 8 | Down | c | .0227 | ||
| ▪HADH | 7 | Down | c | .0228 | ||
| ▪ACAT1 | 8 | Down | .0264 | |||
| ▪PHYH | 7 | Down | c | c | .0302 | |
| ▪ACSL3 | 6 | Up | .0426 | |||
| ▪MLYCD | 8 | Down | c | <.0001 | ||
| Gluconeogenesis | G6PC | 6 | Down | c | c | .0015 |
| PCK1 | 7 | Down | c | .0245 | ||
| PCK2 | 7 | Down | c | <.0001 | ||
| FBP1 | 7 | Down | c | .0013 | ||
| Ketogenesis | ▪BDH1 | 7 | Down | c | .0082 | |
| Amino acid | ▪GCDH | 8 | Down | c | .0005 | |
| ▪PIPOX | 7 | Down | c | .0007 | ||
| ▪AGXT | 8 | Down | c | .0011 | ||
| CDO1 | 7 | Down | c | .0014 | ||
| ▪FAHD2A | 8 | Down | .0015 | |||
| ▪AASS | 7 | Down | c | .0018 | ||
| FTCD | 7 | Down | c | .002 | ||
| ADI1 | 6 | Down | c | .0029 | ||
| DAO | 6 | Down | c | .0038 | ||
| CTH | 7 | Down | c | .0039 | ||
| ▪HAAO | 7 | Down | c | .0039 | ||
| HPD | 7 | Down | c | .0052 | ||
| HGD | 7 | Down | c | .0052 | ||
| BHMT | 7 | Down | c | .0057d | ||
| SARDH | 8 | Down | c | .0079 | ||
| ▪BCKDHA | 7 | Down | .0081 | |||
| MSRA | 8 | Down | .0086 | |||
| ▪HIBCH | 7 | Down | c | .009 | ||
| ▪BHMT2 | 6 | Down | c | .0128 | ||
| ▪BCKDHB | 8 | Down | c | .0135 | ||
| CBS | 8 | Down | c | .0141d | ||
| MAT1A | 8 | Down | c | .0167d | ||
| PAH | 7 | Down | c | .0205 | ||
| ▪THNSL1 | 6 | Down | c | .0256 | ||
| FAH | 7 | Down | c | .0444 | ||
| SUOX | 7 | Down | c | <.0001 | ||
| ▪ALDH18A1 | 7 | Up | c | .02 | ||
| ▪ASNS | 7 | Up | c | .0103d | ||
| ABC transporter | ▪ABCA6 | 7 | Down | c | .0015 | |
| ▪ABCC6 | 8 | Down | c | c | .0106 | |
| Ion transport | ▪KCNJ8 | 7 | Down | c | .0109 | |
| ▪CNGA1 | 7 | Down | c | c | .0002 | |
| ▪ATP1B3 | 7 | Up | c | .0008 | ||
| ▪P2RX4 | 7 | Up | c | .0466 | ||
| ▪SLC39A1 | 7 | Up | .0235 | |||
| CLIC1 | 8 | Up | c | <.0001 | ||
| S.M. transport | ▪SLC25A15 | 7 | Down | c | c | .0003 |
| ▪SLC27A5 | 7 | Down | c | .0003 | ||
| ▪SLC16A2 | 8 | Down | c | .0007 | ||
| ▪SLC25A20 | 8 | Down | c | .001 | ||
| ▪AQP7 | 7 | Down | .0013 | |||
| ▪SLC6A12 | 7 | Down | c | .0015 | ||
| ▪STARD5 | 8 | Down | .0023 | |||
| ▪SLCO2B1 | 7 | Down | c | .0042 | ||
| ▪SLC46A3 | 8 | Down | .0057 | |||
| ▪SLC1A1 | 6 | Down | c | .0266 | ||
| ▪SLC27A2 | 8 | Down | c | .0421 | ||
| ▪SLC47A1 | 7 | Down | c | .0467 | ||
| SLC38A4 | 8 | Down | c | .0066 | ||
| SLC28A1 | 6 | Down | c | .0467 | ||
| AQP9 | 6 | Down | c | .0001 | ||
| SLC2A2 | 7 | Down | c | .0002 | ||
| SLC10A1 | 7 | Down | c | .0005 | ||
| SLC22A7 | 7 | Down | c | c | .0008 | |
| SLC23A2 | 7 | Down | c | .0096 | ||
| SLC22A1 | 8 | Down | .0129d | |||
| ▪SLC2A6 | 6 | Up | c | .0094 | ||
| ▪SLC36A1 | 7 | Up | c | .0338 | ||
| SLC38A1 | 6 | Up | c | .0047 | ||
| SLC29A2 | 6 | Up | .0142 | |||
| SLC7A1 | 8 | Up | c | .0163 | ||
| Multipurpose | ▪ADH6 | 7 | Down | c | .0001 | |
| ▪GOT2 | 7 | Down | c | .0001 | ||
| ▪MAOB | 6 | Down | c | c | .001 | |
| ▪ALDH7A1 | 6 | Down | c | .0011 | ||
| ▪CBR4 | 8 | Down | .004 | |||
| ALDH2 | 8 | Down | c | .0062 | ||
| ▪ALDH9A1 | 7 | Down | c | .0477 | ||
| ADH1B | 7 | Down | c | .0008 | ||
| ALDH6A1 | 8 | Down | c | .0062 | ||
| ADH1C | 6 | Down | c | .0071 | ||
| AKR7A3 | 7 | Down | c | .0169 | ||
| ▪CA12 | 8 | Up | c | .0027 | ||
| Others | ▪SORD | 7 | Down | c | .0003 | |
| ▪MMACHC | 6 | Down | c | .0006 | ||
| ▪HAO1 | 7 | Down | c | .0009 | ||
| ▪DCXR | 7 | Down | c | .002 | ||
| ▪QDPR | 7 | Down | c | .0035 | ||
| ▪PCCB | 6 | Down | c | .0058 | ||
| ▪GFOD2 | 7 | Down | .0059 | |||
| ▪AGL | 8 | Down | c | .009 | ||
| ▪GNE | 8 | Down | c | .0238 | ||
| ▪MTHFD1 | 7 | Down | c | .0254 | ||
| ▪RBKS | 7 | Down | c | .0351 | ||
| ▪ADCY1 | 8 | Down | c | .0375 | ||
| ▪GAMT | 8 | Down | c | .0386 | ||
| UGP2 | 7 | Down | c | .0014 | ||
| ALAS1 | 6 | Down | c | .0027 | ||
| PON3 | 7 | Down | c | .0047 | ||
| RDH16 | 7 | Down | c | .0089 | ||
| ABAT | 8 | Down | c | .0093 | ||
| HAO2 | 8 | Down | .0152d | |||
| GRHPR | 7 | Down | c | <.0001 | ||
| MTHFS | 8 | Down | c | c | .0028 | |
| ▪NNT | 6 | Down | c | .0046 | ||
| ▪MUT | 7 | Down | c | c | .0067 | |
| GLYAT | 7 | Down | c | .0002 | ||
| SULT2A1 | 6 | Down | c | .0002 | ||
| CRYL1 | 7 | Down | c | .0045 | ||
| GNMT | 8 | Down | c | .0009 | ||
| PON1 | 7 | Down | c | .0072 | ||
| ▪NANS | 6 | Up | c | .0009 | ||
| ▪DDAH2 | 8 | Up | c | .001 | ||
| ▪MFSD10 | 7 | Up | c | .0057 | ||
| ▪LTA4H | 8 | Up | .0087 | |||
| ▪GYG1 | 7 | Up | c | .0267 | ||
| SULT1C2 | 8 | Up | .0064 | |||
| AACS | 7 | Up | c | .0069 | ||
| NOX4 | 7 | Up | c | .0422 | ||
| SMS | 6 | Up | c | c | .0328 | |
| SRM | 7 | Up | c | .0006 | ||
Genes categorized as other or multipurpose are those with functions either not yet well defined or not directly connected to a particular metabolic process. Kaplan-Meier overall survival was calculated for each gene and statistical significance analyzed by log-rank (Mantel-Cox) test. Square (▪) indicates novel targets in liver cancer as determined by searching PubMed.
#, number of datasets in which each gene is expressed at P < .05.
All listed metabolic genes correlated with ECM2 and MMP9.
Denotes P value.
Indicates those that also correlated with CDH1 and or VIM (Pearson correlation was considered significant at P < .05).
Previously identified as a survival predictor in hepatocellular carcinoma (HCC) (see the referenced study and other similarly described targets in Supplementary Table 1).