Identification of CDK1 as a Biomarker for the Treatment of Liver Fibrosis and Hepatocellular Carcinoma Through Bioinformatics Analysis
Abstract
1. Introduction
2. Results
2.1. Acquisition of DEGs and the GEO2R Analysis
2.2. Results of the GO KEGG Enrichment Analysis
2.3. Construction of PPI Networks and Screening of Key Hub Genes
2.4. High Expression of CDK1 in HCC Cells Significantly Reduced the Survival Rate of Hepatocellular Carcinoma Patients
2.5. Analysis of Immune Infiltration of CDK1
2.6. Methylation of CDK1 Disables Immunosuppressants in Hepatocellular Carcinoma
2.7. CDK1 Expression Was Positively Correlated with the Grade and Staging of the Tumors
2.8. CDK1 Action Receptor and Active Component of HCC Treatment
2.9. Molecular Docking Results of CDK1 and Active Components
3. Discussion
4. Materials and Method
4.1. Acquisition of RNA-Seq Data of Activated Hepatic Stellate Cells (HSCs)
4.2. The Differential Gene Expression Analysis of the Microarray Data
4.3. Protein Interaction (PPI) Networks of DEGs
4.4. Enrichment Analysis and Functional Annotation of the 2.4 DEGs
4.5. Analysis of Survival Prognosis Related to CDK1
4.6. Analysis of Immune Cell Infiltration
4.7. Analysis of the Interaction of CDK1 with Immunosuppressants and MHC Molecules
4.8. Association Between CDK1 Expression and Stage Grade of Hepatocellular Carcinoma in Human
4.9. Selection of Receptors and Drugs for CDK1 Action in Human Hepatocellular Carcinoma
4.10. Molecular Docking and Kinetic Simulation for the Validation of the Effective Components for the Treatment of Hepatocellular Carcinoma
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene Symbol | adj.p.Val | p Value | t | B | logFC |
---|---|---|---|---|---|
TOP2A | 0.12789 | 0.00535 | 7.3 | −1.89819 | 6.1906911 |
CALD1 | 0.05537 | 0.000559 | 15.8 | 0.85216 | 6.10536365 |
RRM2 | 0.38828 | 0.0432 | 3.38 | −4.55825 | 5.6877799 |
CDK1 | 0.06921 | 0.00108 | 12.7 | 0.08781 | 5.681935 |
ANLN | 0.04192 | 0.000229 | 21.3 | 1.81079 | 5.6470256 |
DLGAP5 | 0.1093 | 0.00366 | 8.33 | −1.4181 | 5.58844865 |
NEK2 | 0.03218 | 0.000111 | 27.2 | 2.50046 | 5.4713496 |
CDKN3 | 0.06542 | 0.000872 | 13.6 | 0.33851 | 5.4477173 |
PRC1 | 0.00433 | 7.92 × 10−8 | 307 | 4.6163 | 5.438704 |
HMMR | 0.11977 | 0.00466 | 7.66 | −1.72192 | 5.4364495 |
TOP2A | 0.10102 | 0.00287 | 9.06 | −1.11079 | 5.34630875 |
APOBEC3B | 0.1972 | 0.0135 | 5.26 | −3.07882 | 5.2771654 |
ASPM | 0.02438 | 0.0000279 | 43.2 | 3.50872 | 5.25215545 |
SHROOM3 | 0.07134 | 0.00123 | 12.1 | −0.07062 | 5.1339738 |
CDK1 | 0.0469 | 0.000364 | 18.3 | 1.32791 | 5.11074285 |
MIR503///MIR424///MIR503HG | 0.26429 | 0.0231 | 4.31 | −3.76446 | 4.9491692 |
CDKN3 | 0.02826 | 0.0000529 | 34.9 | 3.0913 | 4.9007493 |
CDK1 | 0.04122 | 0.000222 | 21.6 | 1.84474 | 4.88621195 |
MYH10 | 0.10263 | 0.003 | 8.92 | −1.16686 | 4.8265022 |
DEPDC1 | 0.02348 | 0.0000137 | 54.8 | 3.86617 | 4.82202725 |
NUF2 | 0.06714 | 0.00096 | 13.2 | 0.22503 | 4.80625185 |
CDC20 | 0.02141 | 0.00000649 | 70.4 | 4.13784 | 4.7577602 |
SHCBP1 | 0.41379 | 0.048 | 3.24 | −4.69101 | 4.746537 |
NUSAP1 | 0.04944 | 0.000412 | 17.5 | 1.19152 | 4.6542621 |
MEGF6 | 0.14361 | 0.00702 | 6.64 | −2.24408 | 4.6460274 |
KIAA0101 | 0.19579 | 0.0133 | 5.29 | −3.05921 | 4.59005025 |
CCNB2 | 0.06324 | 0.000747 | 14.3 | 0.51913 | 4.54231145 |
TK1 | 0.07043 | 0.00116 | 12.4 | 0.00481 | 4.53425635 |
ST6GALNAC5 | 0.04696 | 0.000367 | 18.2 | 1.31903 | 4.4934988 |
TRIP13 | 0.21995 | 0.0166 | 4.87 | −3.34373 | 4.42963645 |
KIF11 | 0.04077 | 0.000217 | 21.7 | 1.86588 | 4.3848553 |
ANLN | 0.07284 | 0.00134 | 11.8 | −0.17191 | 4.37412475 |
UBE2C | 0.09333 | 0.0024 | 9.63 | −0.88967 | 4.129496 |
BIRC5 | 0.02343 | 0.00000957 | 61.8 | 4.00897 | 4.04899235 |
GALNT15 | 0.107 | 0.00348 | 8.48 | −1.35462 | 4.0395688 |
PBK | 0.10906 | 0.00364 | 8.35 | −1.40896 | 4.0233828 |
CCNB1 | 0.18706 | 0.0121 | 5.46 | −2.94424 | 3.98987825 |
SYNPO2 | 0.17546 | 0.0107 | 5.71 | −2.78445 | 3.9871827 |
TK1 | 0.08096 | 0.00175 | 10.7 | −0.49598 | 3.942686 |
ID4 | 0.19244 | 0.0128 | 5.36 | −3.01187 | 3.8204956 |
CEP55 | 0.02348 | 0.0000113 | 58.5 | 3.94689 | 3.8085747 |
CENPH | 0.03812 | 0.000187 | 22.8 | 2.01352 | 3.78016685 |
KNL1 | 0.02538 | 0.0000349 | 40.1 | 3.37228 | 3.74212255 |
COL4A2 | 0.13932 | 0.00662 | 6.78 | −2.16919 | 3.7290946 |
ITGA11 | 0.20015 | 0.014 | 5.19 | −3.12318 | 3.72201025 |
PTN | 0.08079 | 0.00173 | 10.8 | −0.4872 | 3.6569635 |
SORBS1 | 0.17335 | 0.0105 | 5.76 | −2.75316 | 3.60330895 |
OXTR | 0.03626 | 0.000157 | 24.2 | 2.18018 | 3.58367625 |
KIF20A | 0.12046 | 0.00473 | 7.62 | −1.74108 | 3.54996585 |
NREP | 0.186 | 0.012 | 5.48 | −2.92871 | 3.5390412 |
GPAT3 | 0.14374 | 0.00703 | −6.63 | −2.24599 | −4.0068785 |
LRRN3 | 0.02391 | 0.0000265 | −43.9 | 3.53655 | −4.0428889 |
GDF15 | 0.03792 | 0.000179 | −23.2 | 2.05611 | −4.1874975 |
LOC101930400///AKR1C2///AKR1C1 | 0.26356 | 0.023 | −4.32 | −3.75854 | −4.2147407 |
H2BFS | 0.23672 | 0.0191 | −4.63 | −3.52323 | −4.2734285 |
HIST1H4H | 0.0728 | 0.00132 | −11.8 | −0.1598 | −4.2883313 |
KCNJ2 | 0.12826 | 0.00549 | −7.23 | −1.93174 | −4.3042694 |
F2RL1 | 0.04937 | 0.000407 | −17.6 | 1.20609 | −4.3446080 |
MMP10 | 0.1383 | 0.00651 | −6.82 | −2.1471 | −4.3788025 |
CD24 | 0.16218 | 0.00915 | −6.05 | −2.58109 | −4.4126261 |
DUSP6 | 0.06921 | 0.00107 | −12.7 | 0.09775 | −4.4189292 |
MDM2 | 0.03616 | 0.000155 | −24.3 | 2.19471 | −4.4415299 |
CNIH3 | 0.17998 | 0.0113 | −5.61 | −2.84847 | −4.4545942 |
HIST1H2BC///HIST1H2BI///HIST1H2BE///HIST1H2BF///HIST1H2BG | 0.03057 | 0.0000729 | −31.3 | 2.84933 | −4.5961153 |
HIST1H1C | 0.30462 | 0.0292 | −3.94 | −4.06465 | −4.7696097 |
CORO2B | 0.19916 | 0.0138 | −5.21 | −3.11184 | −4.7864721 |
HIST1H2BC | 0.06714 | 0.000945 | −13.2 | 0.24434 | −4.7936413 |
HIST1H4H | 0.17579 | 0.0108 | −5.7 | −2.79027 | −4.8343656 |
MIR146A | 0.03218 | 0.000101 | −28.1 | 2.58075 | −4.8751408 |
PDK4 | 0.07133 | 0.00121 | −12.2 | −0.05298 | −4.8824006 |
CTSS | 0.23602 | 0.019 | −4.64 | −3.51716 | −4.8909467 |
PLAU | 0.08098 | 0.00175 | −10.7 | −0.49883 | −4.9086587 |
RRAD | 0.06324 | 0.000748 | −14.3 | 0.51759 | −4.9342201 |
GK | 0.04656 | 0.00035 | −18.5 | 1.37074 | −4.9782953 |
BTBD11 | 0.11079 | 0.0039 | −8.15 | −1.49722 | −5.0217412 |
CLU | 0.04927 | 0.000402 | −17.7 | 1.22063 | −5.1144443 |
AKR1B10 | 0.05446 | 0.00053 | −16.1 | 0.91266 | −5.1255345 |
CD24 | 0.09974 | 0.0028 | −9.14 | −1.08137 | −5.2352129 |
DCBLD2 | 0.06186 | 0.000702 | −14.6 | 0.59178 | −5.3608140 |
LINC00973 | 0.02391 | 0.0000267 | −43.9 | 3.53382 | −5.4841241 |
MMP1 | 0.13772 | 0.00646 | −6.84 | −2.13708 | −5.5256527 |
AADAC | 0.02391 | 0.0000221 | −46.7 | 3.63589 | −5.5888679 |
SERPIND1 | 0.00966 | 0.00000035 | −186 | 4.56539 | −5.6156946 |
KYNU | 0.06773 | 0.001 | −13 | 0.1743 | −5.6242355 |
ST3GAL6 | 0.03218 | 0.000107 | −27.6 | 2.5333 | −5.7433365 |
PLAU | 0.31948 | 0.0315 | −3.83 | −4.16154 | −5.7927380 |
SLC16A6 | 0.03812 | 0.000186 | −22.9 | 2.01797 | −5.8349129 |
CD24 | 0.07227 | 0.00127 | −12 | −0.11069 | −5.9268551 |
THBD | 0.12169 | 0.00481 | −7.58 | −1.76274 | −5.9403651 |
CD24 | 0.07242 | 0.00128 | −11.9 | −0.12211 | −6.0572334 |
IL13RA2 | 0.04214 | 0.000237 | −21.1 | 1.77762 | −6.3166654 |
CXCL5 | 0.03057 | 0.0000727 | −31.3 | 2.85071 | −6.428763 |
SPP1 | 0.09665 | 0.0026 | −9.37 | −0.99003 | −6.4387306 |
HSD11B1 | 0.04578 | 0.000335 | −18.8 | 1.41684 | −6.5452208 |
NEFL | 0.02141 | 0.00000638 | −70.8 | 4.14284 | −6.9522091 |
MMP3 | 0.27605 | 0.025 | −4.18 | −3.86739 | −7.1158428 |
THBD | 0.02666 | 0.0000419 | −37.7 | 3.25337 | −7.5474292 |
IL24 | 0.05373 | 0.000515 | −16.2 | 0.94497 | −7.646795 |
RAB27B | 0.03057 | 0.0000737 | −31.2 | 2.84013 | −7.6470385 |
EHF | 0.02343 | 0.00000969 | −61.5 | 4.00437 | −7.7647490 |
Parameter | Numerical Value |
---|---|
number of nodes: | 85 |
number of edges: | 447 |
average node degree: | 10.5 |
expected number of edges: | 82 |
PPI enrichment p-value: | <1.0 × 10−16 |
ID | Name | Drug Type | Targets |
---|---|---|---|
DB02052 | Indirubin-3′-Monoxime | Small Molecule | AHR, CDK1, CDK2, CDK5, CDK5R1, GSK3B |
DB02116 | Olomoucine | Small Molecule | CDK1, CDK2, CDK5, MAPK1 |
DB02950 | Hymenialdisine | Small Molecule | CDK1, CDK2, CDK5 |
DB03496 | Alvocidib | Small Molecule | CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, EGFR, PYGB, PYGL,… |
DB04014 | Alsterpaullone | Small Molecule | CDK1, CDK5, GSK3B |
DB06195 | Seliciclib | Small Molecule | CDK1, CDK2, CDK7, CDK9, CSNK1E, MAPK1, MAPK3 |
Active Ingredients | Binding Afinity (eV) |
---|---|
CDK1 | |
Indirubin-3′-Monoxime | −2.6 |
Olomoucine | −6.7 |
Hymenialdisine | −6.3 |
Alvocidib | −8.7 |
Alsterpaullone | −7.8 |
Seliciclib | −8.0 |
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Qin, J.; Li, Z. Identification of CDK1 as a Biomarker for the Treatment of Liver Fibrosis and Hepatocellular Carcinoma Through Bioinformatics Analysis. Int. J. Mol. Sci. 2025, 26, 3816. https://doi.org/10.3390/ijms26083816
Qin J, Li Z. Identification of CDK1 as a Biomarker for the Treatment of Liver Fibrosis and Hepatocellular Carcinoma Through Bioinformatics Analysis. International Journal of Molecular Sciences. 2025; 26(8):3816. https://doi.org/10.3390/ijms26083816
Chicago/Turabian StyleQin, Jiayi, and Zhuan Li. 2025. "Identification of CDK1 as a Biomarker for the Treatment of Liver Fibrosis and Hepatocellular Carcinoma Through Bioinformatics Analysis" International Journal of Molecular Sciences 26, no. 8: 3816. https://doi.org/10.3390/ijms26083816
APA StyleQin, J., & Li, Z. (2025). Identification of CDK1 as a Biomarker for the Treatment of Liver Fibrosis and Hepatocellular Carcinoma Through Bioinformatics Analysis. International Journal of Molecular Sciences, 26(8), 3816. https://doi.org/10.3390/ijms26083816