Identification of APEX2 as an oncogene in liver cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32775374", "kind": "science-record", "revision": 7, "content_hash": "sha256:5ac741f291fe8a2cae74ea33a40c31ba88c1e6f1271d1c576b98cfbc569ef845", "created_at": "2026-11-01T15:41:07Z", "updated_at": "2026-11-01T22:02:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of APEX2 as an oncogene in liver cancer.", "doi": "10.12998/wjcc.v8.i14.2917", "pmid": "32775374", "authors": ["Ru Zheng", "Heng-Liang Zhu", "Bing-Ren Hu", "Xiao-Jiao Ruan", "Hua-Jie Cai"], "journal": "World journal of clinical cases", "year": 2020, "abstract": "BACKGROUND: DNA damage is one of the critical contributors to the occurrence and development of some cancers. APEX1 and APEX2 are the most important molecules in the DNA damage, and APEX1 has been identified as a diagnostic and prognostic biomarker in liver hepatocellular carcinoma (LIHC). However, the expression of APEX2 and its functional mechanisms in LIHC are still unclear.\nAIM: To examine the expression of APEX2 and the potential mechanism network in LIHC.\nMETHODS: We conducted a pan-cancer analysis of the expression of APEX1 and APEX2 using the interactive TIMER tool. GEO datasets, including GSE14520, GSE22058, and GSE64041, were used to compare the APEX2 expression level in tumor tissues and adjacent non-tumor tissues. Then, we calculated the 5-year survival rate according to the web-based Kaplan-Meier analysis. We included the TCGA liver cancer database in GSEA analysis based on the high and low APEX2 expression, showing the potential mechanisms of APEX2 in LIHC. After that, we conducted Pearson correlation analysis using GEPIA2. Next, we performed quantitative polymerase chain reaction (qPCR) assay to examine the APEX2 levels in normal liver cell line LO2 and several liver cancer cell lines, including HepG2, Huh7, SMMC7721, and HCCLM3. APEX2 in HCCLM3 cells was knocked down using small interfering RNA. The role of APEX2 in cell viability was confirmed using CCK-8. Dual-luciferase reporter assay was performed to examine the promoter activity of CCNB1 and MYC.\nRESULTS: APEX1 and APEX2 are both highly expressed in the tumor tissues of BLCA, BRCA, CHOL, COAD, ESCA, HNSC, LIHC, LUAD, LUSC, READ, and STAD. APEX2 overexpression in LIHC was validated using GSE14520, GSE22058, and GSE64041 datasets. The survival analysis showed that LIHC patients with high expression of APEX2 had a lower overall survival rate, even in the AJCC T1 patients. High level of APEX2 could indicate a lower overall survival rate in patients with or without viral hepatitis. The GSEA analysis identified that kinetochore and spindle microtubules are the two main cellular components of APEX2 in GO Ontology. APEX2 was also positively associated with molecular function regulation of chromosome segregation and DNA replication. The results of KEGG analysis indicated that APEX2 expression was positively correlated with cell cycle pathway and pro-oncogenic MYC signaling. Pearson correlation analysis showed that APEX2 had a significant positive correlation with CCNB1 and MYC. APEX2 level was higher in liver cancer cell lines than in normal liver LO2 cells. Small interfering RNA could knock down the APEX2 expression in HCCLM3 cells. Knockdown of APEX2 resulted in a decrease in the viability of HCCLM3 cells as well as the expression and promoter activity of CCNB1 and MYC.\nCONCLUSION: APEX2 is overexpressed in LIHC, and the higher APEX2 level is associated with a worse prognosis in overall survival. APEX2 is closely involved in the biological processes of chromosome segregation and DNA replication. APEX2 expression is positively correlated with the pro-oncogenic pathways. Knockdown of APEX2 could inhibit the cell viability and CCNB1 and MYC pathways, suggesting that APEX2 is an oncogene in LIHC, which could be a potential pharmaceutic target in the anti-tumor therapy.", "claims": [{"id": "claim-method", "statement": "The Kaplan Meier method was used to analyze the overall survival, and the log-rank P method was applied to show the statistical difference.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32775374", "locator": "sections[12] \"Statistical analysis\" paragraph 2", "quote": "The Kaplan Meier method was used to analyze the overall survival, and the log-rank P method was applied to show the statistical difference."}], "state": "complete"}, {"id": "claim-data-access", "statement": "No additional data are available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32775374", "locator": "sections[30] \"Footnotes\" paragraph 2", "quote": "No additional data are available."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32775374"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE14520"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE14520"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32775374", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.12998/wjcc.v8.i14.2917", "sha256": 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For in vitro studies, we performed qPCR to analyze the level of relative gene expres"], "order_basis": "paper_text_order:1124", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["d several liver cancer cell lines, including HepG2, Huh7, SMMC7721, and HCCLM3. APEX2 in HCCLM3", "pe Culture Collection (ATCC). LO2 cells were cultured in RMPI-1640, and HepG2, SMMC7721, Huh7, and HC", "HepG2, SMMC7721, Huh7, and HCCLM3 cells were cultured in DMEM, supplemented with 10% FBS and 100 U/mL", "demy of Science. The liver cancer cell lines HepG2 and Huh7 were acquired from American Type Cu"], "order_basis": "paper_text_order:1241", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["APEX2 in cell viability was confirmed using CCK-8. Dual-luciferase reporter assay was performe", "ring RNA. The cell viability was tested with CCK-8. The promoter activity was detected by dual-"], "order_basis": "paper_text_order:1401", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["k down the APEX2 expression in HCCLM3 cells. Knockdown of APEX2 resulted in a decrease in the viabi", "correlated with the pro-oncogenic pathways. Knockdown of APEX2 could inhibit the cell viability an", "MATERIALS AND METHODS Cell culture and transfection The normal liver cell line LO2 and liver can", "streptomycin. Small interfering RNA (siRNA) transfection was conducted with Lipofectamine 2000 accord"], "order_basis": "paper_text_order:2654", "id": "assay:4"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["logrank_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The Kaplan Meier method was used to analyze the overall survival, and the log-rank P method was applied to show the statistical difference."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}