Construction of a CCL20-centered circadian-signature based prognostic model in cervical cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37183243", "kind": "science-record", "revision": 3, "content_hash": "sha256:4d3f916130e9a7b1e363558c5687c8ba14c15e04e633a0858cba9ebd013c3eb7", "created_at": "2026-11-01T19:01:52Z", "updated_at": "2026-11-01T22:09:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction of a CCL20-centered circadian-signature based prognostic model in cervical cancer.", "doi": "10.1186/s12935-023-02926-6", "pmid": "37183243", "authors": ["Yuchong Yu", "Yao Liu", "Yuhong Li", "Xiaoming Yang", "Mi Han", "Qiong Fan"], "journal": "Cancer cell international", "year": 2023, "abstract": "BACKGROUND: Rather low vaccination rates for Human papillomavirus (HPV) and pre-existing cervical cancer patients with limited therapeutic strategies ask for more precise prognostic model development. On the other side, the clinical significance of circadian clock signatures in cervical cancer lacks investigation.\nMETHODS: Subtypes classification based upon eight circadian clock core genes were implemented in TCGA-CESC through k-means clustering methods. Afterwards, KEGG, GO and GSEA analysis were conducted upon differentially expressed genes (DEGs) between high and low-risk groups, and tumor microenvironment (TME) investigation by CIBERSORT and ESTIMATE. Furthermore, a prognostic model was developed by cox and lasso regression methods, and verified in GSE44001 by time-dependent receiver-operating characteristic curve (ROC) analysis. Lastly, FISH and IHC were used for validation of CCL20 expression in patients' specimens and U14 subcutaneous tumor models were built for TME composition.\nRESULTS: We successfully classified cervical patients into high-risk and low-risk groups based upon circadian-oscillation-signatures. Afterwards, we built a prognostic risk model composed of GJB2, CCL20 and KRT24 with excellent predictive value on patients' overall survival (OS). We then proposed metabolism unbalance, especially for glycolysis, and immune related pathways to be major enriched signatures between the high-risk and low-risk groups. Then, we proposed an 'immune-desert'-like suppressive myeloid cells infiltration pattern in high-risk group TME and verified its resistance to immunotherapies. Finally, CCL20 was proved positively correlated with real-world patients' stages and induced significant less CD8+ T cells and more M2 macrophages infiltration in mouse model.\nCONCLUSIONS: We unraveled a prognostic risk model based upon circadian oscillation and verified its solidity. Specifically, we unveiled distinct TME immune signatures in high-risk groups.", "claims": [{"id": "claim-method", "statement": "Furthermore, a prognostic model was developed by cox and lasso regression methods, and verified in GSE44001 by time-dependent receiver-operating characteristic curve (ROC) analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37183243", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Furthermore, a prognostic model was developed by cox and lasso regression methods, and verified in GSE44001 by time-dependent receiver-operating characteristic curve (ROC) analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data associated with this study are present in the paper or the Supplementary Materials. 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After publication, all reasonable requests for materials, data, and code will be fulfilled after completion of a material transfer agreement between the International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:37183243"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE44001"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE44001"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37183243", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12935-023-02926-6", "sha256": "sha256:0654e00279bb2452b373e658d9d906a93bc7d038b20afec2ea0cd252e896ce4c", "bytes": 85056, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12935-023-02926-6", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10184429", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE44001", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE44001", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE44001", "version": null, "note": "All data associated with this study are present in the paper or the Supplementary Materials. 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Lastly, FISH and IHC were used for validation of CCL20 expression", "of fluorescent spots using ImageJ software. Immunohistochemistry (IHC) analysis of FFPE tissue samples FFPE s", "using ImageJ software. Immunohistochemistry (IHC) analysis of FFPE tissue samples FFPE sectio", "sections from the biopsies were subjected to IHC by using multiplex IHC kit (Panovue, Beijing"], "order_basis": "paper_text_order:914", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ells and more M2 macrophages infiltration in mouse model. CONCLUSIONS: We unraveled a prognostic risk", "ells and more M2 macrophages infiltration in mouse model. CONCLUSIONS: We unraveled a prognosti", "ain reliable survival data of mice, up to 33 mice were breeded in multiple cages at different floor", "en by qRT-PCR and western blot verification. Mice were subcutaneously injected with 0.5 × 106 U14 c"], "order_basis": "paper_text_order:1825", "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": 0.99, "evidence": ["verexpression of ccl20 in U14 cell lines and flow cytometry analysis of subcutaneous mouse tumor model U", ", and tumors were harvested and digested for flow cytometry analysis with antibodies as follows: CD45-Ap", "ful overexpression by qRT-PCR, western blot, flow cytometry and IHC (Additional file 1: Figure S5).Then", "rse survival in CCL20-OE mice (Fig. 10E). By flow cytometry analysis of TME, elevated ratio of M2/M1 was"], "order_basis": "paper_text_order:5714", "id": "assay:3"}, {"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": ["HB-PB-500) for 24 h. After 48 h, cells were cultured with 2 μg/mL puromycin (Sangon Biotech, Shanghai,"], "order_basis": "paper_text_order:6753", "id": "assay:4"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ion within 21 days and chosen by qRT-PCR and western blot verification. Mice were subcutaneously injec", "ed the successful overexpression by qRT-PCR, western blot, flow cytometry and IHC (Additional file 1:", "or overexpression (OE-CCL20) (right); (B) is western blot (WB) plot of NC (left) or OE (right), with H"], "order_basis": "paper_text_order:6963", "id": "assay:5"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Student t-test"], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}