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pmid:37789880
RAD51AP1 as an Immune-Related Prognostic Biomarker and Therapeutic Response Predictor in Hepatocellular Carcinoma.
Yongguang Wei · Chenlu Lan · Xiangkun Wang · Xin Zhou · Xiwen Liao · Huasheng Huang · Zhongliu Wei · Tianman Li · Tao Peng · Guangzhi Zhu
International journal of general medicine · 2023 doi:10.2147/IJGM.S431206
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Experiment
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Complete file
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However, the immune-infiltrating correlation and the therapeutics guidance of RAD51AP1 in hepatocellular carcinoma (HCC) still need further investigation.\nMethods: In this study, comprehensive bioinformatic analysis of RAD51AP1 on differential expression, clinicopathologic correlation, prognostic value, and function enrichment were performed in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO; GSE14520 and GSE76427), and International Cancer Genome Consortium (ICGC) datasets. Besides, the Guangxi cohort containing 50 pairs HCC and adjacent non-cancerous samples from First Affiliated Hospital of Guangxi Medical University was served as validation cohort. Moreover, we explored the predictive value of RAD51AP1 to therapeutics response and its underlying correlation with HCC immunoinfiltration.\nResults: RAD51AP1 was significantly overexpressed in HCC tissues and had a high diagnostic value of HCC. The shorter survival time and poorer clinical features were showed when RAD51AP1 upregulated, and then a nomogram featuring RAD51AP1 expression and other clinicopathologic factors was established to predict prognosis. In CIBERSORT analysis, higher T cells follicular helper but lower T cells CD4+ memory resting infiltration levels were exhibited when RAD51AP1 upregulated. The ssGSEA analysis demonstrated that high-RAD51AP1 expression subgroup had higher macrophages, Th2 and Treg cells infiltration levels, but lower type II IFN response function. Furthermore, high-RAD51AP1 expression subgroup exhibited the upregulated expression levels of immune-related checkpoint genes, but lower IPS and TIDE scores which suggested a possibly better immunotherapy response. The drug sensitivity analysis showed the high-expression subgroup may be more susceptible to Bexarotene, Doxorubicin, Gemcitabine and Tipifarnib.\nConclusion: Taken together, RAD51AP1 is a potential diagnostic and prognostic biomarker. It may be related to the immunosuppressive microenvironment and could be an underlying HCC treatment strategy. However, the conclusions still require further validation studies.", "claims": [{"id": "claim-method", "statement": "The prognostic value of RAD51AP1 was explored preliminarily by Kaplan–Meier survival analysis in TCGA-HCC cohort and was validated in the GSE14520 and ICGC cohorts.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37789880", "locator": "sections[4] \"Differential Expression and Prognostics Value Analysis\" paragraph 2", "quote": "The prognostic value of RAD51AP1 was explored preliminarily by Kaplan–Meier survival analysis in TCGA-HCC cohort and was validated in the GSE14520 and ICGC cohorts."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All raw online RNA sequencing dataset and clinical information of HCC patients, which were included in the current study, can be downloaded from the TCGA (https://portal.gdc.cancer.gov/), ICGC (http://dcc.icgc.org), and GEO database (https://www.ncbi.nlm.nih.gov/geo/). Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37789880", "locator": "sections[22] \"Data Sharing Statement\" paragraph 2", "quote": "All raw online RNA sequencing dataset and clinical information of HCC patients, which were included in the current study, can be downloaded from the TCGA (https://portal.gdc.cancer.gov/), ICGC (http://dcc.icgc.org), and GEO database (https://www.ncbi.nlm.nih.gov/geo/). Further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "High RAD51AP1 expression was associated with poorer overall and recurrence-free survival in HCC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37789880", "locator": "sections[13] \"RAD51AP1 Correlated with Dismal Survival and Poor Clinical Features\" paragraph 2", "quote": "The survival analysis suggested that the high RAD51AP1-expression group showed a poorer OS and recurrence free survival (RFS) than that of the low expression group in the TCGA cohorts (Figure 2A and B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "High RAD51AP1 expression was associated with poorer overall and recurrence-free survival in HCC.", "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:37789880"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "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:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon", "step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37789880", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/IJGM.S431206", "sha256": "sha256:79fa22935c06560f89ff5db0730f6e55d66aa04606d36bc0920f73d8194cca3e", "bytes": 43435, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/IJGM.S431206", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10543100", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-2", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman correlation"}}, {"id": "method-3", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "chi-square"}}, {"id": "method-4", "family": null, "specific": null, "label": "Kaplan–Meier survival analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The prognostic value of RAD51AP1 was explored preliminarily by Kaplan–Meier survival analysis in TCGA-HCC cohort and was validated in the GSE14520 and ICGC cohorts."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "method.group_comparison_wilcoxon"]}, "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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