Integrative bioinformatics analysis identifies ROBO1 as a potential therapeutic target modified by miR-218 in hepatocellular carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:28977866", "kind": "science-record", "revision": 8, "content_hash": "sha256:391a7c197cc1e746f015fbd7672fc2482bbdeeda3c07bd9d9781d529c7ced72a", "created_at": "2026-11-01T15:40:28Z", "updated_at": "2026-11-01T21:59:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrative bioinformatics analysis identifies ROBO1 as a potential therapeutic target modified by miR-218 in hepatocellular carcinoma.", "doi": "10.18632/oncotarget.18099", "pmid": "28977866", "authors": ["Junqing Wang", "Yunyun Zhou", "Xiaochun Fei", "Xunhua Chen", "Rui Chen", "Zhenggang Zhu", "Yongjun Chen"], "journal": "Oncotarget", "year": 2017, "abstract": "Patients diagnosed with advanced hepatocellular carcinoma (HCC) presented poor prognosis and short survival time. Althouth accumulating contribution of continuous research has gradually revealed complex tumorigenesis mechanism of HCC with numerous and jumbled biomarkers, those specific ones for HCC diagnose and therapeutic treatment are required illustration. Multiple genes over-expressed in HCC specimens with at least 1.5 fold change were cohorted, compared with the non-cancerous tissues through integrative bioinformatics analysis from Gene Expression Omnibus (GEO) datasets GSE14520 and GSE6764, including 445 and 45 cases of samples spearatly, along with intensive exploration on the Cancer Genome Altas (TCGA) dataset of liver cancer. Thirteen genes significantly highly expressed, overlapping in the datasets above. The Database for Annotation Visualization and Integrated Discovery (DAVID) program was utilized for functional pathway enrichment analysis. Protein-protein Interaction (PPI) analysis was conducted through the Search Tool for the Retrieval of Interacting Genes (STRING) database. ROBO1 was highlighted as one of the most probable molecules among the 13 candidates participating in cancer process. Cancer Cell Line Encycolopedia (CCLE) database was utilized exploring ROBO1 expression in cell lines. Immunochemistry analysis and qRT-PCR assay were performed in our medical center, which indicates significant over-expression status in either HCC tumor specimens and 3 HCC cell lines. Furtherly, we recognized that miR-218, a tumor suppressor, might be an upstream regulator for ROBO1 directly binding to the mRNA 3'UTR and potentially modifying the expression and function of ROBO1. Herein, we conclude that ROBO1 is a mighty therapeutic targets modified by miR-218 in HCC deserving further investigation.", "claims": [{"id": "claim-method", "statement": "P values were calculated by paired t-test and Fisher’s exact text.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28977866", "locator": "sections[15] \"Statistical analysis\" paragraph 2", "quote": "P values were calculated by paired t-test and Fisher’s exact text."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profile dataset GSE14520 and GSE6764 was downloaded from GEO database (https://www.ncbi.nlm.nih.gov/geo/). Platforms of GEO datasets are GPL3921 (Affymetrix HT Human Genome U133A Array) for GSE14520 dataset and GPL570 (Affymetrix Human Genome U133 Plus 2.0 Array) (Agilent Technologies, Santa Clara, CA, USA) for GSE6764. In GSE14520 dataset, there consists of 445 samples derived from HCC patients (225 tumor tissues and 220 non-cancerous tissues).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28977866", "locator": "sections[9] \"Gene expression profile data\" paragraph 2", "quote": "The gene expression profile dataset GSE14520 and GSE6764 was downloaded from GEO database (https://www.ncbi.nlm.nih.gov/geo/). Platforms of GEO datasets are GPL3921 (Affymetrix HT Human Genome U133A Array) for GSE14520 dataset and GPL570 (Affymetrix Human Genome U133 Plus 2.0 Array) (Agilent Technologies, Santa Clara, CA, USA) for GSE6764. In GSE14520 dataset, there consists of 445 samples derived from HCC patients (225 tumor tissues and 220 non-cancerous tissues)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using paired t-tests and Fisher’s exact test, the study found that ROBO1 is highly expressed in HCC tissues and cell lines and is directly downregulated post-transcriptionally by miR-218.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:28977866", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Herein, we conclude that ROBO1 is a mighty therapeutic targets modified by miR-218 in HCC deserving further investigation."}, {"asset": "source:pmid:28977866", "locator": "sections[15] \"Statistical analysis\" paragraph 2", "quote": "Data from GEO and TCGA database was processed as mentioned above. Results derived from samples and cells were statistically analyzed by using SPSS 18.0. P values were calculated by paired t-test and Fisher’s exact text. P values < 0.05 were considered statistically significant."}, {"asset": "source:pmid:28977866", "locator": "sections[7] \"DISCUSSION\" paragraph 4", "quote": "In our study, we downloaded datasets of HCC patients’ information and gene expression data from NCBI GEO database (GSE14520 and GSE6764) and TCGA database."}, {"asset": "source:pmid:28977866", "locator": "sections[10] \"DEGs identification\" paragraph 3", "quote": "The online database of Cancer Cell Line Encyclopedia (CCLE: https://portals.broadinstitute.org) was applied to determine the expression level of candidate gene among differential HCC cell lines."}, {"asset": "source:pmid:28977866", "locator": "sections[12] \"Cell culture and surgical specimens\" paragraph 3", "quote": "Twenty-three pairs of HCC cancer specimens along with the adjacent non-cancerous tissues were collected from HCC patients performed partial hepatectomy without preoperative therapy at the Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine within 2015."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using paired t-tests and Fisher’s exact test, the study found that ROBO1 is highly expressed in HCC tissues and cell lines and is directly downregulated post-transcriptionally by miR-218.", "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:28977866"], "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. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE14520", "GSE6764"], "resolved_accessions": ["GSE14520", "GSE6764"], "statements": ["The gene expression profile dataset GSE14520 and GSE6764 was downloaded from GEO database (https://www.ncbi.nlm.nih.gov/geo/). Platforms of GEO datasets are GPL3921 (Affymetrix HT Human Genome U133A Array) for GSE14520 dataset and GPL570 (Affymetrix Human Genome U133 Plus 2.0 Array) (Agilent Technologies, Santa Clara, CA, USA) for GSE6764. In GSE14520 dataset, there consists of 445 samples derived from HCC patients (225 tumor tissues and 220 non-cancerous tissues)."], "basis": "The paper names GSE14520, GSE6764 in NCBI GEO database and the accession resolves in the repository. 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All cells were cultured in RPMI 1640 supplemented with 10% heat-inactiv", "SG-7701 and three HCC cell lines (SMMC-7721, HePG2 and HeP3B) were purchased from Shanghai Inst"], "order_basis": "paper_text_order:2061", "id": "assay:1"}, {"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["Protein-protein Interaction"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}