Figures
Figure 1. The positive and negative screen of CRISPR screen experiment. CRISPR: clustered regularly interspaced short palindromic repeats.
Figure 2. The expression level of ZW10 within primary malignancies. (a) mRNA expression status. (b) Protein expression status. (c) Immunohistochemical staining picture. ACC: adrenocortical carcinoma; BLCA: bladder urothelial carcinoma; BRCA: breast invasive carcinoma; CESC: cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: cholangiocarcinoma; COAD: colon adenocarcinoma; DLBC: lymphoid neoplasm diffuse large B-cell lymphoma; ESCA: esophageal carcinoma; GBM: glioblastoma multiforme; HNSC: head and neck squamous cell carcinoma; KICH: kidney chromophobe; KIRC: kidney renal clear cell carcinoma; KIRP: kidney renal papillary cell carcinoma; LAML: acute myeloid leukemia; LGG: brain lower grade glioma; LIHC: liver hepatocellular carcinoma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; MESO: mesothelioma; OV: ovarian serous cystadenocarcinoma; PAAD: pancreatic adenocarcinoma; PCPG: pheochromocytoma and paraganglioma; PRAD: prostate adenocarcinoma; READ: rectum adenocarcinoma; SARC: sarcoma; SKCM: skin cutaneous melanoma; STAD: stomach adenocarcinoma; TGCT: testicular germ cell tumors; THCA: thyroid carcinoma; THYM: thymoma; UCEC: uterine corpus endometrial carcinoma; UCS: uterine carcinosarcoma; UVM: uveal melanoma.
Figure 3. The survival analysis of ZW10 across various cancers. (a) Overall survival analysis. (b) Disease-specific survival analysis. (c) Disease-free interval analysis. (d) Progression-free interval analysis.
Figure 4. Integrated analysis of ZW10 mRNA expression level. (a) Forest plot of standardized mean difference. (b) Summary receiver operating characteristic curve. (c) Egger funnel plot (P = 0.115).
Figure 5. Etiology stratification analysis in different subgroups. (a) Alcohol consumption. (b) Hepatitis (B or C). (c) Hepatitis B. (d) Hepatitis C. (e) The combination of alcohol consumption and hepatitis (B or C). (f) Non-alcoholic fatty liver disease. (g) Inflammation status of adjacent hepatic tissue.
Figure 6. The association between ZW10 mRNA expression status and clinical parameters. (a) Age. (b) Gender. (c) Race. (d) Primary stage. (e) AJCC stage. (f) Overall survival. **P < 0.01, nsP > 0.05. AJCC: American Joint Committee on Cancer.
Figure 7. Gene effect of ZW10 for 20 HCC cell lines based on the DepMap database. HCC: hepatocellular carcinoma.
Figure 8. The differences of the predicted half-maximal inhibitory concentration of TKIs in ZW10-high expression and ZW10-low expression groups. (a) Axitinib. (b) Bosutinib. (c) Erlotinib. (d) Lapatinib. (e) Sunitinib. (f) Dasatinib. (g) Gefitinib. (h) Imatinib. (i) Nilotinib. (j) Sorafenib. IC50: half-maximal inhibitory concentration; TKIs: tyrosine kinase inhibitors.
Figure 9. Functional enrichment analysis for ZW10 strongly related and differentially expressed genes.
Figure 10. Differential analyses between ZW10 expression and the microenvironment characteristics. ***P < 0.001, **P < 0.01, *P < 0.05.
Figure 11. Structure of mocetinostat (a), lypressin (b), and indatraline (c). The structures of the three compounds were downloaded from the PubChem database.
Figure 12. Three-dimensional and two-dimensional interaction networks of mocetinostat, capecitabine, and ZW10 protein. (a) Mocetinostat binding to ZW10 protein. (b) Capecitabine binding to ZW10 protein.
Tables
Table 1. Risk Factors Analysis for HCC Based on the TCGA-LIHC Dataset
| Variables | HR (95% CI) | P-value |
|---|
| AJCC: American Joint Committee on Cancer; CI: confidence interval; HCC: hepatocellular carcinoma; HR: hazard ratio. |
| ZW10 (continuous) | 1.05 (1.02 - 1.07) | < 0.01 |
| Age (> 65 vs. ≤ 65) | 1.14 (0.78 - 1.67) | 0.49 |
| Gender (male vs. female) | 0.76 (0.52 - 1.12) | 0.17 |
| Race (Asian vs. not-Asian) | 0.81 (0.55 - 1.20) | 0.30 |
| pT (pT3 + pT4 vs. pT1 + pT2) | 2.47 (1.68 - 3.61) | < 0.01 |
| AJCC stage (III + IV vs. I + II) | 2.45 (1.67 - 3.58) | < 0.01 |
Table 2. The Top Three Compounds Opposing ZW10 and Their Affinity to ZW10 Protein
| Compound | Description | Score | PubChem CID | Minimum binding energy with ZW10 |
|---|
| HDAC: histone deacetylase. |
| Mocetinostat | HDAC inhibitor | -99.93 | 9865515 | -8.2 kcal/mol |
| Lypressin | Vasopressin receptor agonist | -99.89 | 644076 | -7.6 kcal/mol |
| Indatraline | Norepinephrine transporter inhibitor | -99.89 | 126280 | -7.0 kcal/mol |