World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website https://www.wjon.org

Original Article

Volume 15, Number 6, December 2024, pages 882-901

ACTR10 Overexpression Facilitates the Progression and Tyrosine Kinase Inhibitor Resistance in Hepatocellular Carcinoma

Figures

Figure 1.
Figure 1. Flow chart of ACTR10 mRNA dataset screening. GEO: Gene Expression Omnibus; GTEx: Genotype-Tissue Expression; ICGC: International Cancer Genome Consortium; SRA: Sequence Read Archive; TCGA: The Cancer Genome Atlas.
Figure 2.
Figure 2. Integrated analysis of the expression of ACTR10 in HCC. (a) Forest plot showing the high expression of ACTR10 in HCC tissues compared to non-HCC liver tissues. (b, c) Plots showing the results of Egger’s and Begg’s tests, which showed that there was no publication bias. HCC: hepatocellular carcinoma; SMD: standardized mean difference.
Figure 3.
Figure 3. Integrated analysis of the diagnostic performance of ACTR10 in HCC. (a) The AUC of the sROC curve was 0.69 (95% CI: 0.65 - 0.73), with a sensitivity of 0.52 (95% CI: 0.44 - 0.61) and a specificity of 0.78 (95% CI: 0.69 - 0.85). (b) The combined sensitivity was 0.52 (95% CI: 0.44 - 0.61). (c) The combined specificity was 0.78 (95% CI: 0.69 - 0.85). (d) The combined positive DLR was 2.37 (95% CI: 1.85 - 3.05). (e) The combined negative DLR was 0.61 (95% CI: 0.54 - 0.69). AUC: area under the curve; CI: confidence interval; DLR: diagnostic likelihood ratio; HCC: hepatocellular carcinoma; sROC: summary receiver operating characteristic.
Figure 4.
Figure 4. The distribution of ACTR10 mRNA expression in different HCC cell lines. The abscissa represents the distribution of ACTR10 mRNA expression (TPM) and the ordinate represents the different HCC cell lines. HCC: hepatocellular carcinoma.
Figure 5.
Figure 5. The gene effect scores for the ACTR10 gene in the 19 HCC cell lines. The abscissa represents the gene effect score of ACTR10 in each HCC cell line and the ordinate represents the 19 HCC cell lines. HCC: hepatocellular carcinoma.
Figure 6.
Figure 6. Analyses of the potential pathogenic molecular mechanisms of ACTR10 in HCC. (a) Intersecting genes were identified by overlapping the HCC OEGs and ACTR10 CEGs. (b) The intersecting genes were subjected to GO functional enrichment. (c) The intersecting genes were subjected to KEGG signal pathway analysis. (d) The intersecting genes were subjected to Reactome signal pathway analysis. CEGs: co-expressed genes; GO: Gene Ontology; HCC: hepatocellular carcinoma; KEGG: Kyoto Encyclopedia of Genes and Genomes; OEGs: overexpressed genes.
Figure 7.
Figure 7. Flow chart showing the process used to screen and select the datasets for the survival analysis. GEO: Gene Expression Omnibus; GTEx: Genotype-Tissue Expression; ICGC: International Cancer Genome Consortium; SRA: Sequence Read Archive; TCGA: The Cancer Genome Atlas.
Figure 8.
Figure 8. The resultant forest plot showed that ACTR10 was a risk factor for HCC patients. HCC: hepatocellular carcinoma; HR: hazard ratio.
Figure 9.
Figure 9. Flow chart showing the process used to screen and select the datasets for the transcriptome-level TKI-resistance analysis. GEO: Gene Expression Omnibus; GTEx: Genotype-Tissue Expression; ICGC: International Cancer Genome Consortium; SRA: Sequence Read Archive; TCGA: The Cancer Genome Atlas; TKI: tyrosine kinase inhibitor.
Figure 10.
Figure 10. Integrated analysis of the expression of ACTR10 in TKI-resistant HCC. (a) Forest plot showing the high expression of ACTR10 in TKI-resistant HCC samples compared to TKI-sensitive samples. (b, c) The results of Egger’s and Begg’s tests showed that there was no publication bias. HCC: hepatocellular carcinoma; TKI: tyrosine kinase inhibitor.
Figure 11.
Figure 11. Integrated analysis of the diagnostic performance of ACTR10 in TKI-resistant HCC. (a) The AUC of the sROC curve was 0.99 (95% CI: 0.98 - 1.00), with a sensitivity of 0.99 (95% CI: 0.61 - 1.00) and a specificity of 0.73 (95% CI: 0.23 - 0.96). (b) The combined sensitivity was 0.99 (95% CI: 0.61 - 1.00). (c) The combined specificity was 0.73 (95% CI: 0.23 - 0.96). (d) The combined positive DLR was 3.71 (95% CI: 0.74 - 18.58). (e) The combined negative DLR was 0.01 (95% CI: 0.00 - 0.80). AUC: area under the curve; CI: confidence interval; DLR: diagnostic likelihood ratio; HCC: hepatocellular carcinoma; sROC: summary receiver operating characteristic; TKI: tyrosine kinase inhibitor.
Figure 12.
Figure 12. Molecular docking model of trichostatin A and ACTR10 (affinity energy = -8.1 kcal/mol).

Tables

Table 1. Information on the ACTR10 mRNA Datasets
 
StudyNHCCMHCCSDHCCNnon-HCC liverMnon-HCC liverSDnon-HCC liver
NHCC: the number of HCC samples; MHCC: the mean expression level of ACTR10 in HCC samples; SDHCC: the standard deviation of ACTR10 expression in HCC samples; Nnon-HCC liver: the number of non-HCC liver samples; Mnon-HCC liver: the mean expression level of ACTR10 in non-HCC liver samples; SDnon-HCC liver: the standard deviation of ACTR10 expression in non-HCC liver samples; HCC: hepatocellular carcinoma.
E_MTAB_8887233.410.77173.480.99
GPL105585236.350.334036.230.31
GPL111542453.100.991682.900.89
GPL136673386.640.443426.530.34
GPL14951938.250.45187.800.59
GPL16043251.270.64251.310.57
GPL167912095.031.191144.560.94
GPL175861016.530.24896.300.14
GPL185732152.742.55131.591.56
GPL20301483.091.74302.411.21
GPL20795384.660.96384.170.56
GPL21047103.380.11103.350.07
GPL246764064.011.521353.321.30
GPL41331811.710.911810.890.76
GPL5175483.110.06483.060.04
GPL5708445.310.265285.300.21
GPL571963.280.051313.270.04
GPL6244663.830.12753.800.10
GPL6480833.570.04823.560.03
GPL69471043.290.09973.300.06
GPL9052604.430.55604.290.49
GSE114783107.841.72268.801.48
GSE11501812-1.850.4812-1.860.16
GSE145202253.270.082203.180.09
GSE16616335.960.4236.441.69
GSE20140358.950.27348.850.15
GSE2205810010.880.349710.810.19
GSE22405243.250.17243.150.15
GSE250972683.030.162893.010.09
GSE3329433.430.2533.080.11
GSE46444886.901.03487.310.91
GSE50579672.900.13102.810.11
GSE5504843.020.3942.600.26
GSE56545213.310.07213.320.03
GSE575555-0.180.025-0.150.03
GSE59259810.840.54810.970.22
GSE605021810.730.451810.370.30
GSE677643-1.160.206-1.360.12
ICGC_LIRI_JP2403.162.431972.932.21
TCGA_GTEx_HCC3714.060.562763.920.58

 

Table 2. Information on the Datasets Used for the Survival Analysis
 
StudyHCCPlatform
HCC: hepatocellular carcinoma.
E-TABM-3641Affymetrix HG-U133A GeneChips arrays
GSE7642790GPL10558
TCGA-LIHC321RNA-seq

 

Table 3. Information on the Datasets Used in the Transcriptome-Level TKI-Resistance Analysis
 
StudyNTKI-SMTKI-SSDTKI-SNTKI-RMTKI-RSDTKI-R
TKI: tyrosine kinase inhibitor; TKI-S: TKI-sensitive; TKI-R: TKI-resistant.
GSE121153510.160.14310.060.03
GSE12907133.710.6634.551.03
GSE14323334.940.1834.670.64
GSE158458_146.310.1345.500.26
GSE158458_247.100.2446.550.10
GSE17615135.370.2535.140.29
GSE18619135.620.1035.270.08
GSE18971139.780.1939.380.20
GSE23464733.442.0234.471.70
GSE73571_149.880.07310.240.04
GSE73571_239.600.0739.530.10
GSE94550610.390.05310.250.05

 

Table 4. Potential Drugs Targeting ACTR10 in DGB Database
 
Cell lineTimeDoseP-valueq-valuelogFoldChangeSpecificity
DGB: Drug Gene Budger.
Trichostatin AMCF76 h0.1 µM00-1.350950.000249563
Trichostatin AHL606 h0.1 µM5.33468 × 10-385.22588×10-36-1.070170.000342466
Trichostatin AHL606 h1.0 µM1.35366 × 10-131.00243×10-11-1.744510.000390778