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
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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. 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 1.
↓  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 2.
↓  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 3.
↓  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 4.
↓  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 5.
↓  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 6.
↓  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 7.
↓  Figure 8. The resultant forest plot showed that ACTR10 was a risk factor for HCC patients. HCC: hepatocellular carcinoma; HR: hazard ratio.
Figure 8.
↓  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 9.
↓  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 10.
↓  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 11.
↓  Figure 12. Molecular docking model of trichostatin A and ACTR10 (affinity energy = -8.1 kcal/mol).
Figure 12.

Tables

↓  Table 1. Information on the ACTR10 mRNA Datasets
 
Study NHCC MHCC SDHCC Nnon-HCC liver Mnon-HCC liver SDnon-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_8887 23 3.41 0.77 17 3.48 0.99
GPL10558 523 6.35 0.33 403 6.23 0.31
GPL11154 245 3.10 0.99 168 2.90 0.89
GPL13667 338 6.64 0.44 342 6.53 0.34
GPL14951 93 8.25 0.45 18 7.80 0.59
GPL16043 25 1.27 0.64 25 1.31 0.57
GPL16791 209 5.03 1.19 114 4.56 0.94
GPL17586 101 6.53 0.24 89 6.30 0.14
GPL18573 215 2.74 2.55 13 1.59 1.56
GPL20301 48 3.09 1.74 30 2.41 1.21
GPL20795 38 4.66 0.96 38 4.17 0.56
GPL21047 10 3.38 0.11 10 3.35 0.07
GPL24676 406 4.01 1.52 135 3.32 1.30
GPL4133 18 11.71 0.91 18 10.89 0.76
GPL5175 48 3.11 0.06 48 3.06 0.04
GPL570 844 5.31 0.26 528 5.30 0.21
GPL571 96 3.28 0.05 131 3.27 0.04
GPL6244 66 3.83 0.12 75 3.80 0.10
GPL6480 83 3.57 0.04 82 3.56 0.03
GPL6947 104 3.29 0.09 97 3.30 0.06
GPL9052 60 4.43 0.55 60 4.29 0.49
GSE114783 10 7.84 1.72 26 8.80 1.48
GSE115018 12 -1.85 0.48 12 -1.86 0.16
GSE14520 225 3.27 0.08 220 3.18 0.09
GSE166163 3 5.96 0.42 3 6.44 1.69
GSE20140 35 8.95 0.27 34 8.85 0.15
GSE22058 100 10.88 0.34 97 10.81 0.19
GSE22405 24 3.25 0.17 24 3.15 0.15
GSE25097 268 3.03 0.16 289 3.01 0.09
GSE33294 3 3.43 0.25 3 3.08 0.11
GSE46444 88 6.90 1.03 48 7.31 0.91
GSE50579 67 2.90 0.13 10 2.81 0.11
GSE55048 4 3.02 0.39 4 2.60 0.26
GSE56545 21 3.31 0.07 21 3.32 0.03
GSE57555 5 -0.18 0.02 5 -0.15 0.03
GSE59259 8 10.84 0.54 8 10.97 0.22
GSE60502 18 10.73 0.45 18 10.37 0.30
GSE67764 3 -1.16 0.20 6 -1.36 0.12
ICGC_LIRI_JP 240 3.16 2.43 197 2.93 2.21
TCGA_GTEx_HCC 371 4.06 0.56 276 3.92 0.58

 

↓  Table 2. Information on the Datasets Used for the Survival Analysis
 
Study HCC Platform
HCC: hepatocellular carcinoma.
E-TABM-36 41 Affymetrix HG-U133A GeneChips arrays
GSE76427 90 GPL10558
TCGA-LIHC 321 RNA-seq

 

↓  Table 3. Information on the Datasets Used in the Transcriptome-Level TKI-Resistance Analysis
 
Study NTKI-S MTKI-S SDTKI-S NTKI-R MTKI-R SDTKI-R
TKI: tyrosine kinase inhibitor; TKI-S: TKI-sensitive; TKI-R: TKI-resistant.
GSE121153 5 10.16 0.14 3 10.06 0.03
GSE129071 3 3.71 0.66 3 4.55 1.03
GSE143233 3 4.94 0.18 3 4.67 0.64
GSE158458_1 4 6.31 0.13 4 5.50 0.26
GSE158458_2 4 7.10 0.24 4 6.55 0.10
GSE176151 3 5.37 0.25 3 5.14 0.29
GSE186191 3 5.62 0.10 3 5.27 0.08
GSE189711 3 9.78 0.19 3 9.38 0.20
GSE234647 3 3.44 2.02 3 4.47 1.70
GSE73571_1 4 9.88 0.07 3 10.24 0.04
GSE73571_2 3 9.60 0.07 3 9.53 0.10
GSE94550 6 10.39 0.05 3 10.25 0.05

 

↓  Table 4. Potential Drugs Targeting ACTR10 in DGB Database
 
Cell line Time Dose P-value q-value logFoldChange Specificity
DGB: Drug Gene Budger.
Trichostatin A MCF7 6 h 0.1 µM 0 0 -1.35095 0.000249563
Trichostatin A HL60 6 h 0.1 µM 5.33468 × 10-38 5.22588×10-36 -1.07017 0.000342466
Trichostatin A HL60 6 h 1.0 µM 1.35366 × 10-13 1.00243×10-11 -1.74451 0.000390778