Identification of aberrantly methylated differentially expressed genes and pro-tumorigenic role of KIF2C in melanoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35991567", "kind": "science-record", "revision": 4, "content_hash": "sha256:4bc1f032f489c47a3df85386704b2d09ea55a5f64e1ddb4d35066d7877bd89ec", "created_at": "2026-11-01T18:15:08Z", "updated_at": "2026-11-01T22:07:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of aberrantly methylated differentially expressed genes and pro-tumorigenic role of KIF2C in melanoma.", "doi": "10.3389/fgene.2022.817656", "pmid": "35991567", "authors": ["Chun-Hui Huang", "Wei Han", "Yi-Zhu Wu", "Guo-Liang Shen"], "journal": "Frontiers in genetics", "year": 2022, "abstract": "Background: Skin Cutaneous Melanoma (SKCM) is known as an aggressive malignant cancer, which could be directly derived from melanocytic nevi. However, the molecular mechanisms underlying the malignant transformation of melanocytes and melanoma tumor progression still remain unclear. Increasing research showed significant roles of epigenetic modifications, especially DNA methylation, in melanoma. This study focused on the identification and analysis of methylation-regulated differentially expressed genes (MeDEGs) between melanocytic nevus and malignant melanoma in genome-wide profiles. Methods: The gene expression profiling datasets (GSE3189 and GSE114445) and gene methylation profiling datasets (GSE86355 and GSE120878) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified via GEO2R. MeDEGs were obtained by integrating the DEGs and DMGs. Then, a functional enrichment analysis of MeDEGs was performed. STRING and Cytoscape were used to describe the protein-protein interaction (PPI) network. Furthermore, survival analysis was implemented to select the prognostic hub genes. Next, we conducted gene set enrichment analysis (GSEA) of hub genes. To validate, SKCM cell culture and lentivirus infection was performed to reveal the expression and behavior pattern of KIF2C. Patients and specimens were collected and then immunohistochemistry (IHC) staining was conducted. Results: We identified 237 hypomethylated, upregulated genes and 182 hypermethylated, downregulated genes. Hypomethylation-upregulated genes were enriched in biological processes of the oxidation-reduction process, cell proliferation, cell division, phosphorylation, extracellular matrix disassembly and protein sumoylation. Pathway enrichment showed selenocompound metabolism, small cell lung cancer and lysosome. Hypermethylation-downregulated genes were enriched in biological processes of positive regulation of transcription from RNA polymerase II promoter, cell adhesion, cell proliferation, positive regulation of transcription, DNA-templated and angiogenesis. The most significantly enriched pathways involved the transcriptional misregulation in cancer, circadian rhythm, tight junction, protein digestion and absorption and Hippo signaling pathway. After PPI establishment and survival analysis, seven prognostic hub genes were CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2, and FBL. Moreover, the most involved hallmarks obtained by GSEA were E2F targets, G2M checkpoint and mitotic spindle. Importantly, among the 7 hub genes, we found that down-regulated level of KIF2C expression significantly inhibited the proliferative ability of SKCM cells and suppressed the metastasis capacity of SKCM cells. Conclusions: Our study identified potential aberrantly methylated-differentially expressed genes participating in the process of malignant transformation from nevus to melanoma tissues based on comprehensive genomic profiles. Transcription profiles of CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2, and FBL provided clues of aberrantly methylation-based biomarkers, which might improve the development of precision medicine. KIF2C plays a pro-tumorigenic role and potentially inhibited the proliferative ability in SKCM.", "claims": [{"id": "claim-method", "statement": "In the present study, GEO2R was used to identify the differentially expressed genes (DEGs) as well as the differentially methylated genes (DMGs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35991567", "locator": "sections[4] \"Identification of methylation-regulated differentially expressed genes\" paragraph 2", "quote": "In the present study, GEO2R was used to identify the differentially expressed genes (DEGs) as well as the differentially methylated genes (DMGs)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We downloaded the gene expression profiling datasets generated by high-throughput sequencing (GSE3189 and GSE114445) and the microarray-based gene methylation profiling datasets (GSE120878 and GSE86355) from the Gene Expression Omnibus database (GEO, https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35991567", "locator": "sections[3] \"Acquisition and standardization of raw microarray dataset\" paragraph 2", "quote": "We downloaded the gene expression profiling datasets generated by high-throughput sequencing (GSE3189 and GSE114445) and the microarray-based gene methylation profiling datasets (GSE120878 and GSE86355) from the Gene Expression Omnibus database (GEO, https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified seven prognostic hub genes: CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2, and FBL.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35991567", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "After PPI establishment and survival analysis, seven prognostic hub genes were CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2, and FBL."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified seven prognostic hub genes: CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2, and FBL.", "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:35991567"], "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": ["GSE3189", "GSE114445", "GSE86355", "GSE120878"], "resolved_accessions": ["GSE3189", "GSE114445", "GSE86355", "GSE120878"], "statements": ["We downloaded the gene expression profiling datasets generated by high-throughput sequencing (GSE3189 and GSE114445) and the microarray-based gene methylation profiling datasets (GSE120878 and GSE86355) from the Gene Expression Omnibus database (GEO, https://www.ncbi.nlm.nih.gov/geo/)."], "basis": "The paper names GSE3189, GSE114445, GSE86355, GSE120878 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pearson_r"], "assets": ["source:pmid:35991567", "data:geo:GSE114445"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE114445"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:00:55Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 11984, "completion_tokens": 1895, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:35991567", "type": "paper", "label": "pmid:35991567"}, {"id": "source:pmid:35991567", "type": "manuscript", "label": "PMID 35991567 full text"}, {"id": "data:geo:GSE114445", "type": "dataset", "label": "GEO GSE114445"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35991567", "type": "paper", "label": "pmid:35991567"}, {"id": "source:pmid:35991567", "type": "manuscript", "label": "PMID 35991567 full text"}, {"id": "data:geo:GSE114445", "type": "dataset", "label": "GEO GSE114445"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35991567", "type": "extraction", "used": ["source:pmid:35991567"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE114445", "type": "accession_resolution", "used": ["data:geo:GSE114445"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:35991567", "parent_hash": "sha256:fe116acd7fe6b91ca1a612f090d38cbd508986824a20efcc2b3da86dad6dfe05", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE114445 licence not read", "asset:data:geo:GSE114445 not downloaded", "asset:data:geo:GSE120878 licence not read", "asset:data:geo:GSE120878 not downloaded", "asset:data:geo:GSE3189 licence not read", "asset:data:geo:GSE3189 not downloaded", "asset:data:geo:GSE86355 licence not read", "asset:data:geo:GSE86355 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["tients and specimens were collected and then immunohistochemistry (IHC) staining was conducted. Results: We id", "ere collected and then immunohistochemistry (IHC) staining was conducted. Results: We identif", "S1Validation of the KIF2C role in SKCM. (A) IHC analysis was performed to reveal high expres"], "order_basis": "paper_text_order:1509", "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": 0.77, "evidence": ["ences (Shanghai, China). The SKCM cells were cultured in RPMI 1640 medium (Gibco, CA, United States)"], "order_basis": "paper_text_order:4804", "id": "assay:2"}, {"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": ["from GeneChem (Shanghai, China). Cells were transfected and underwent sterility testing with lentivi", "< 0.001). (C) qRT-PCR was used to detect the knockdown efficacy of siRNAs silencing expression of K", "entiviral vectors and small interfering RNA (siRNA; siRNA-1: 5′-GCC​CAC​TGA​ATA​AGC​AAG​AAT-3';", "al vectors and small interfering RNA (siRNA; siRNA-1: 5′-GCC​CAC​TGA​ATA​AGC​AAG​AAT-3'; siRNA-"], "order_basis": "paper_text_order:5187", "id": "assay:3"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["groups. (D) According to the results of the CCK-8 assay, down-regulated level of KIF2C express"], "order_basis": "paper_text_order:8954", "id": "assay:4"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pearson_r"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Pearson correlation"], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}