Identification and validation of Cystatin A as a novel promising therapeutic target for gastric cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38989439", "kind": "science-record", "revision": 3, "content_hash": "sha256:fafcf5ea14ff92c171cce4a6a708d891ed4b91943a7b7050f0b931204bff8db1", "created_at": "2026-11-01T20:29:03Z", "updated_at": "2026-11-01T22:12:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of Cystatin A as a novel promising therapeutic target for gastric cancer.", "doi": "10.21037/jgo-23-941", "pmid": "38989439", "authors": ["Qingyu Xu", "Shuai Xue", "Yaqiong Zhang", "Jian Li", "Peiyu Qian", "Yanyan Zhang", "Li Feng"], "journal": "Journal of gastrointestinal oncology", "year": 2024, "abstract": "Background: The effect of pharmacological treatment of gastric cancer (GC) is limited, thus, it holds significant scientific importance to thoroughly investigate the molecular mechanisms underlying GC development and identify novel molecules capable of substantially extending patients' survival. This study utilized bioinformatics techniques to identify 11 genes associated with recurrence-free survival (RFS) in GC patients and investigated the potential biological functions of these genes through single-cell transcriptomic analysis. Subsequently, a single gene Cystatin A (CSTA) was selected for further analysis to explore its impact on signaling pathways and treatment.\nMethods: Differentially expressed genes (DEGs) were identified and overlapped in the analysis of RFS to identify potential prognostic genes for GC patients, based on data from the Cancer Genome Atlas-stomach adenocarcinoma (TCGA-STAD) and GSE54129. Subsequently, a prognostic model based on RFS in GC patients was established. Single-cell sequencing data were employed to explore the potential functions of these model genes. CSTA, one of the RFS-related genes, was further investigated using immunohistochemistry (IHC), Cell Counting Kit 8 (CCK-8), transwell, scratch, colony formation assays, flow cytometry, and Western blotting methods.\nResults: Through bioinformatics analysis, we identified 23 RFS-related genes in GC. Using the least absolute shrinkage and selection operator (LASSO)-Cox method, an RFS prognostic model was developed which pinpointed 11 GC prognosis-related (GPR) genes as significant factors influencing RFS in GC patients. The single-cell analysis revealed their potential role in affecting differentiation and maturation of pre-fibroblasts thereby impacting RFS in GC patients. CSTA exhibited low expression levels in GC tissues. Overexpression of CSTA promoted apoptosis in GC cells through the caspase-dependent apoptotic pathway and enhanced their response to cisplatin via this same pathway.\nConclusions: The 11 GPR genes are primarily enriched within a specific type of stromal cell exhibiting heightened communication, metabolism, and differentiation levels. The gene signature of these stromal cells has implications for patient prognosis. Additionally, CSTA, a gene related to prognosis, has been shown to influence apoptosis levels in GC cells.", "claims": [{"id": "claim-method", "statement": "To assess the prognostic value of the 23 overlapping genes, we then conducted a least absolute shrinkage and selection operator (LASSO)-Cox regression analysis to evaluate the association between each gene and survival status in TCGA cohort.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38989439", "locator": "sections[6] \"Development of a prognostic risk-score model in TCGA cohort\" paragraph 2", "quote": "To assess the prognostic value of the 23 overlapping genes, we then conducted a least absolute shrinkage and selection operator (LASSO)-Cox regression analysis to evaluate the association between each gene and survival status in TCGA cohort."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-941/dss", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38989439", "locator": "sections[29] \"Footnotes\" paragraph 2", "quote": "Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-941/dss"}], "state": "complete"}, {"id": "claim-target-result", "statement": "Through bioinformatics analysis, we identified 23 RFS-related genes in GC. 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Using the least absolute shrinkage and selection operator (LASSO)-Cox method, an RFS prognostic model was developed which pinpointed 11 GC prognosis-related (GPR) genes as significant factors influencing RFS in GC patients.", "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:38989439"], "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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Overexpression of CSTA promoted apoptosis in GC cells through the caspase-dependent ap", "ed to prognosis, has been shown to influence apoptosis levels in GC cells.", "nohistochemistry (IHC), Cell Counting Kit 8 (CCK-8), transwell, scratch, colony formation assay", "A promoted apoptosis in GC cells through the caspase-dependent apoptotic pathway and enhanced the"], "order_basis": "paper_text_order:1278", "id": "assay:2"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["transwell, scratch, colony formation assays, flow cytometry, and Western blotting methods. Results: Thro"], "order_basis": "paper_text_order:1331", "id": "assay:3"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["colony formation assays, flow cytometry, and Western blotting methods. Results: Through bioinformatics ana"], "order_basis": "paper_text_order:1351", "id": "assay:4"}, {"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": ["re obtained from the CRL-1740 Lncap. The AGS cell line was cultured in Dulbecco’s Modified Eagle Medium (DMEM),", "ified Eagle Medium (DMEM), while the SGC7901 cell line was cultured in Roswell Park Memorial Institute (RPMI) 16", "om the CRL-1740 Lncap. 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