Meta-analysis of expression and the targeting of cell adhesion associated genes in nine cancer types - A one research lab re-evaluation.

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These characteristics determine inherent and acquired resistance, which need to be overcome for improving patient survival. In line with the global efforts in identifying druggable resistance factors, extensive preclinical research of the Cordes lab and others designated the cancer adhesome as a critical and general therapy resistance mechanism with multiple druggable cancer targets. In our study, we addressed pancancer cell adhesion mechanisms by connecting the preclinical datasets generated in the Cordes lab with publicly available transcriptomic and patient survival data. We identified similarly changed differentially expressed genes (scDEGs) in nine cancers and their corresponding cell models relative to normal tissues. Those scDEGs interconnected with 212 molecular targets from Cordes lab datasets generated during two decades of research on adhesome and radiobiology. Intriguingly, integrative analysis of adhesion associated scDEGs, TCGA patient survival and protein-protein network reconstruction revealed a set of overexpressed genes adversely affecting overall cancer patient survival and specifically the survival in radiotherapy-treated cohorts. This pancancer gene set includes key integrins (e.g. ITGA6, ITGB1, ITGB4) and their interconnectors (e.g. SPP1, TGFBI), affirming their critical role in the cancer adhesion resistome. In summary, this meta-analysis demonstrates the importance of the adhesome in general, and integrins together with their interconnectors in particular, as potentially conserved determinants and therapeutic targets in cancer.", "claims": [{"id": "claim-method", "statement": "Patient survival analyses for corresponding low- and high-expression patient cohorts were performed in R by log-rank testing for each gene in each cancer type independently with three p-value cutoffs (p < 0.1; p < 0.05; p < 0.01) to indicate the degree of significance.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37206618", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "Patient survival analyses for corresponding low- and high-expression patient cohorts were performed in R by log-rank testing for each gene in each cancer type independently with three p-value cutoffs (p < 0.1; p < 0.05; p < 0.01) to indicate the degree of significance."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Survival and expression data of nine TCGA datasets (LUSC, LUAD, PRAD, COAD, READ, LGG, GBM, HNSCC, PAAD) were obtained from the Xena platform [34] and evaluated.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37206618", "locator": "sections[7] \"Survival analysis\" paragraph 2", "quote": "Survival and expression data of nine TCGA datasets (LUSC, LUAD, PRAD, COAD, READ, LGG, GBM, HNSCC, PAAD) were obtained from the Xena platform [34] and evaluated."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We identified similarly changed differentially expressed genes (scDEGs) in nine cancers and their corresponding cell models relative to normal tissues.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37206618", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We identified similarly changed differentially expressed genes (scDEGs) in nine cancers and their corresponding cell models relative to normal tissues."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "We identified similarly changed differentially expressed genes (scDEGs) in nine cancers and their corresponding cell models relative to normal tissues.", "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:37206618"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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