Molecular Signature of Small Cell Lung Cancer after Treatment Failure: The MCM Complex as Therapeutic Target.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33801812", "kind": "science-record", "revision": 8, "content_hash": "sha256:97a3e9302bce535b442df1483e8885c5d614e2c814bf1c3f8a361f03ba07ce9b", "created_at": "2026-11-01T15:41:31Z", "updated_at": "2026-11-01T22:46:26Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Molecular Signature of Small Cell Lung Cancer after Treatment Failure: The MCM Complex as Therapeutic Target.", "doi": "10.3390/cancers13061187", "pmid": "33801812", "authors": ["Shunsuke Misono", "Keiko Mizuno", "Takayuki Suetsugu", "Kengo Tanigawa", "Nijiro Nohata", "Akifumi Uchida", "Hiroki Sanada", "Reona Okada", "Shogo Moriya", "Hiromasa Inoue", "Naohiko Seki"], "journal": "Cancers", "year": 2021, "abstract": "Small cell lung cancer (SCLC) is a highly aggressive cancer, and patients who become refractory to first-line treatment have a poor prognosis. The development of effective treatment regimens is urgently needed. In this study, we identified a gene expression signature of SCLC after treatment failure using SCLC clinical specimens (GEO accession number: GSE162102). A total of 1,136 genes were significantly upregulated in SCLC tissues. These upregulated genes were subjected to KEGG pathway analysis, and \"cell cycle\", \"Fanconi anemia\", \"alcoholism\", \"systemic lupus erythematosus\", \"oocyte meiosis\", \"homologous recombination\", \"DNA replication\", and \"p53 signaling\" were identified as the enriched pathways among the genes. We focused on the cell cycle pathway and investigated the clinical significance of four genes associated with this pathway: minichromosome maintenance (MCM) 2, MCM4, MCM6, and MCM7. The overexpression of these MCM genes was confirmed in SCLC clinical specimens. Knockdown assays using siRNAs targeting each of these four MCM genes showed significant attenuation of cancer cell proliferation. Moreover, siRNA-mediated knockdown of each MCM gene enhanced the cisplatin sensitivity of SCLC cells. Our SCLC molecular signature based on SCLC clinical specimens after treatment failure will provide useful information to identify novel molecular targets for this disease.", "claims": [{"id": "claim-method", "statement": "One-way analysis of variance (ANOVA) and Tukey’s post-hoc test were used for multiple group comparisons.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33801812", "locator": "sections[9] \"2.7. 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Normal lung tissues", "n = 4", ""], ["Sample name", "Tissue", "case no."], ["SCLC N-1", "Normal lung tissue", "1"], ["SCLC N-2", "Normal lung tissue", "1"], ["SCLC N-3", "Normal lung tissue", "2"], ["SCLC N-4", "Normal lung tissue", "3"]], "row_count": 16, "column_count": 3, "numeric_cells": 26, "header_rows": 2, "locator": "section[11]/table-wrap[2]#cancers-13-01187-t002"}}, {"id": "asset:table:pmid:33801812:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2fc7ee31f72069d53d480c068c322d35e5f88a17d2978c8086fb2a1854207683", "bytes": 812, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#cancers-13-01187-t003", "version": null, "note": "Significantly enriched annotations of the upregulated genes identified by microarray expression analysis of SCLC clinical specimens.", "structure": {"pmcid": "PMC7998124", "section_index": 12, "section_title": "3.2. mRNA Expression Signature of SCLC after Treatment Failure", "row_count": 9, "column_count": 3}, "table": {"label": "Table 3", "caption": "Significantly enriched annotations of the upregulated genes identified by microarray expression analysis of SCLC clinical specimens.", "rows": [["No. of Genes", "p-Value", "Annotations"], ["28", "2.28 × 10−12", "(KEGG) 04110: Cell cycle"], ["15", "9.66 × 10−8", "(KEGG) 03460: Fanconi anemia pathway"], ["26", "6.19 × 10−7", "(KEGG) 05034: Alcoholism"], ["21", "2.12 × 10−6", "(KEGG) 05322: Systemic lupus erythematosus"], ["18", "7.67 × 10−5", "(KEGG) 04114: Oocyte meiosis"], ["10", "8.54 × 10−5", "(KEGG) 03440: Homologous recombination"], ["9", "1.92 × 10−4", "(KEGG) 03030: DNA replication"], ["10", "1.21 × 10−2", "(KEGG) 04115: p53 signaling pathway"]], "row_count": 9, "column_count": 3, "numeric_cells": 24, "header_rows": 1, "locator": "section[12]/table-wrap[1]#cancers-13-01187-t003"}}, {"id": "asset:table:pmid:33801812:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a38bbcfd82365419f3069de61c2c1b7aea858836495f48f502beff23e1bd25e1", "bytes": 2911, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#cancers-13-01187-t004", "version": null, "note": "Upregulated genes associated with the cell cycle pathway.", "structure": {"pmcid": "PMC7998124", "section_index": 13, "section_title": "3.3. Expression of MCM2, MCM4, MCM6, MCM7 in SCLC Tissues", "row_count": 30, "column_count": 8}, "table": {"label": "Table 4", "caption": "Upregulated genes associated with the cell cycle pathway.", "rows": [["", "", "", "", "Normalized Read Count (Log2)"], ["EntrezGeneID", "GeneSymbol", "Gene Name", "Location", "Log2FoldChange", "NormalLungTissues", "SCLCTissues", "p-Value"], ["7272", "TTK", "TTK protein kinase", "6q14.1", "3.67", "−0.37", "3.30", "0.0034"], ["9134", "CCNE2", "cyclin E2", "8q22.1", "3.57", "0.05", "3.62", "0.0002"], ["4173", "MCM4", "minichromosome maintenance complex component 4", "8q11.21", "3.33", "0.20", "3.54", "0.0004"], ["699", "BUB1", "budding uninhibited by benzimidazoles 1 homolog", "2q13", "3.18", "−0.25", "2.92", "0.0040"], ["701", "BUB1B", "budding uninhibited by benzimidazoles 1 homolog beta", "15q15.1", "3.08", "−0.03", "3.05", "0.0018"], ["9133", "CCNB2", "cyclin B2", "15q22.2", "3.05", "0.05", "3.10", "0.0055"], ["1029", "CDKN2A", "cyclin-dependent kinase inhibitor 2A", "9p21.3", "3.01", "0.24", "3.25", "0.0047"], ["4171", "MCM2", "minichromosome maintenance complex component 2", "3q21.3", "2.96", "0.01", "2.97", "0.0008"], ["995", "CDC25C", "cell division cycle 25 homolog C", "5q31.2", "2.87", "−0.01", "2.87", "0.0045"], ["891", "CCNB1", "cyclin B1", "5q13.2", "2.82", "−0.06", "2.76", "0.0008"], ["1869", "E2F1", "E2F transcription factor 1", "20q11.22", "2.82", "−0.30", "2.52", "0.0100"], ["9700", "ESPL1", "extra spindle pole bodies homolog 1", "12q13.13", "2.70", "0.10", "2.80", "0.0007"], ["8318", "CDC45", "cell division cycle 45 homolog", "22q11.21", "2.64", "−0.29", "2.34", "0.0027"], ["8317", "CDC7", "cell division cycle 7 homolog", "1p22.2", "2.62", "0.01", "2.63", "0.0006"], ["4085", "MAD2L1", "MAD2 mitotic arrest deficient-like 1", "4q27", "2.61", "−0.19", "2.42", "0.0013"], ["898", "CCNE1", "cyclin E1", "19q12", "2.61", "0.06", "2.67", "0.0041"], ["1111", "CHEK1", "CHK1 checkpoint homolog", "11q24.2", "2.57", "0.00", "2.57", "0.0088"], ["993", "CDC25A", "cell division cycle 25 homolog A", "3p21.31", "2.50", "−0.15", "2.34", "0.0044"], ["9232", "PTTG1", "pituitary tumor-transforming 1", "5q33.3", "2.40", "0.07", "2.47", "0.0030"], ["983", "CDK1", "cyclin-dependent kinase 1", "10q21.2", "2.40", "0.05", "2.45", "0.0058"], ["10926", "DBF4", "DBF4 homolog", "7q21.12", "2.22", "0.06", "2.28", "0.0002"], ["4176", "MCM7", "minichromosome maintenance complex component 7", "7q22.1", "2.20", "0.13", "2.33", "0.0002"], ["890", "CCNA2", "cyclin A2", "4q27", "2.17", "0.03", "2.20", "0.0141"], ["4175", "MCM6", "minichromosome maintenance complex component 6", "2q21.3", "2.05", "−0.11", "1.94", "0.0002"], ["6502", "SKP2", "S-phase kinase-associated protein 2 (p45)", "5p13.2", "2.04", "0.23", "2.27", "0.0117"], ["5111", "PCNA", "proliferating cell nuclear antigen", "20p13", "2.04", "0.01", "2.05", "0.0017"], ["5591", "PRKDC", "protein kinase, DNA-activated, catalytic polypeptide", "8q11.21", "2.01", "−0.03", "1.98", "0.0071"], ["10744", "PTTG2", "pituitary tumor-transforming 2", "4p14", "2.00", "−0.01", "1.99", "0.0084"]], "row_count": 30, "column_count": 8, "numeric_cells": 189, "header_rows": 2, "locator": "section[13]/table-wrap[1]#cancers-13-01187-t004"}}], "gaps": ["asset:data:geo:GSE162102 not downloaded", "asset:data:geo:GSE162102 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "One-way analysis of variance (ANOVA) and Tukey’s post-hoc test were used for multiple group comparisons."}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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Knockdown assays using siRNAs targeting each of these", "cell proliferation. Moreover, siRNA-mediated knockdown of each MCM gene enhanced the cisplatin sens", "tion of cancer cell proliferation. Moreover, siRNA-mediated knockdown of each MCM gene enhanced", "ownregulation of MCM family members by siRNA transfection in SCLC cells, Figure S6: Apoptosis data obt"], "order_basis": "paper_text_order:1053", "id": "assay:1"}, {"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": ["s, Figure S2: Histopathological findings and immunohistochemical analyses of MCM2, MCM4, MCM6, and MCM7 in ca", "2, Figure S3: Histopathological findings and immunohistochemical analyses of MCM2, MCM4, MCM6, and MCM7 in ca", "3, Figure S4: Histopathological findings and immunohistochemical analyses of MCM2, MCM4, MCM6, and MCM7 in no", "ds 3.1. 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