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pmid:38136595
Identification of a Prognostic Signature for Ovarian Cancer Based on Ubiquitin-Related Genes Suggesting a Potential Role for FBXO9.
Xiaomei Luo · Yingjie Wang · Hao Zhang · Guangquan Chen · Jindan Sheng · Xiu Tian · Renhao Xue · Yu Wang
Biomolecules · 2023 doi:10.3390/biom13121724
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Complete file
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Ubiquitin-related genes (UbRGs) are involved in the initiation and progression of cancers, but have still not been utilized for diagnosis and prognosis of OV.\nMETHODS: K48-linked ubiquitination in ovarian tissues from our OV and control cohort was assessed using immunohistochemistry. UbRGs, including ubiquitin and ubiquitin-like regulators, were screened based on the TCGA-OV and GTEx database. Univariate Cox regression analysis identified survival-associated UbRGs. A risk model was established using the LASSO regression and multivariate Cox regression analysis. The relationship between UbRGs and immune cell infiltration, tumor mutational burden, drug sensitivity, and immune checkpoint was determined using the CIBERSORT, ESTIMATE, and Maftools algorithms, based on the Genomics of Drug Sensitivity in Cancer and TCGA-OV databases. GEPIA2.0 was used to analyze the correlation between FBXO9/UBD and DNA damage repair-related genes. Finally, FBXO9 and UBD were accessed in tissues or cells using immunohistochemistry, qPCR, and Western blot.\nRESULTS: We confirmed the crucial role for ubiquitination in OV as a significant decrease of K48-linked ubiquitination was observed in primary OV lesions. We identified a prognostic signature utilizing two specific UbRGs, FBXO9 and UBD. The risk score obtained from this signature accurately predicted the overall survival of TCGA-OV training dataset and GSE32062 validation dataset. Furthermore, this risk score also showed association with immunocyte infiltration and drug sensitivity, revealing potential mechanisms for ubiquitination mediated OV risk. In addition, FBXO9, but not UBD, was found to be downregulated in OV and positively correlated with DNA damage repair pathways, suggesting FBXO9 as a potential cancer suppressor, likely via facilitating DNA damage repair.\nCONCLUSIONS: We identified and validated a signature of UbRGs that accurately predicts the prognosis, offers valuable guidance for optimizing chemotherapy and targeted therapies, and suggests a potential role for FBXO9 in OV.", "claims": [{"id": "claim-method", "statement": "A risk model was established using the LASSO regression and multivariate Cox regression analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38136595", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A risk model was established using the LASSO regression and multivariate Cox regression analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/geo/, accessed on 11 September 2023), the UCSC Xena database (https://xenabrowser.net/, accessed on 11 September 2023), the GTEx database (https://www.gtexportal.org/, accessed on 11 September 2023), the STRING database (https://string-db.org/, accessed on 11 September 2023), and the GDSC database (https://www.cancerrxgene.org/, accessed on 11 September 2023), which is an updating, openly available resource for free download. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE32062"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "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:GSE32062"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38136595", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/biom13121724", "sha256": "sha256:1123a3df3853b165fba995b32738a3ca445a7240da048c9e701595d5e8c5c3a0", "bytes": 49828, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/biom13121724", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10742228", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE32062", "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=GSE32062", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE32062", "version": null, "note": "The datasets analyzed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/geo/, accessed on 11 September 2023), the UCSC Xena database (https://xenabrowser.net/, accessed on 11 September 2023), the GTEx database (https://www.gtexportal.org/, accessed on 11 September 2023), the STRING database (https://string-db.org/, accessed on 11 September 2023), and the GDSC database (https://www.cancerrxgene.org/, accessed on 11 September 2023), which is an updating, openly available resource for free download. 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UbRGs, including ubiquitin and ubiquitin-li", "UBD were accessed in tissues or cells using immunohistochemistry, qPCR, and Western blot. RESULTS: We confirm"], "order_basis": "paper_text_order:476", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["tissues or cells using immunohistochemistry, qPCR, and Western blot. RESULTS: We confirmed the"], "order_basis": "paper_text_order:1238", "id": "assay:2"}, {"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": ["cells using immunohistochemistry, qPCR, and Western blot. RESULTS: We confirmed the crucial role for"], "order_basis": "paper_text_order:1249", "id": "assay:3"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["of immune checkpoint genes. According to the RNA-sequencing expression profiles of the TCGA-OV cohort, w", "he sequential process of our research study. Transcriptome profiles and clinical characteristics of TCG", "vival (OS) were excluded from the study. The transcriptome profiles of normal ovarian tissue (n = 88) w"], "order_basis": "paper_text_order:3073", "id": "assay:4"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["A risk model was established using the LASSO regression and multivariate Cox regression analysis."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}