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pmid:33269607
Oncogenic Roles of RAD51AP1 in Tumor Tissues Related to Overall Survival and Disease-Free Survival in Hepatocellular Carcinoma.
Liping Zhuang · Yuan Zhang · Zhiqiang Meng · Zongguo Yang
Cancer control : journal of the Moffitt Cancer Center · 2020 doi:10.1177/1073274820977149
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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The Liver Hepatocellular Carcinoma (TCGA, Provisional) and GSE36376 datasets were used for survival analysis. RAD51AP1 associations with clinicopathological features were determined with the GSE36376 dataset.\nRESULTS: RAD51AP1 mRNA expression was significantly upregulated in advanced liver fibrosis samples (S3-4 vs. S0-2 and G3-4 vs. G0-2) from hepatitis B virus (HBV)-related liver fibrosis patients and in tumor tissues and peripheral blood mononuclear cells (PBMCs) from HCC patients (all P < 0.05). HCC patients with high RAD51AP1 expression had significantly worse overall survival (OS) and disease-free survival (DFS) than those with low RAD51AP1 expression (P = 0.0034 and P = 0.0012, respectively) in the TCGA dataset, and these findings were validated with the GSE36376 dataset (P = 0.0074 and P = 0.0003, respectively). A Cox regression model indicated that RAD51AP1 was a risk factor for OS and DFS in HCC patients in GSE36376 (HR = 1.54, 95% CI = 1.02-2.32, P = 0.04 and HR = 1.71, 95% CI = 1.22-2.39, P = 0.002, respectively). Moreover, RAD51AP1 mRNA expression increased gradually with increasing tumor stage, including stratification by American Joint Committee on Cancer (AJCC) stages, Barcelona Clinic Liver Cancer (BCLC) stages and Edmondson grades. In addition, RAD51AP1 was overexpressed in HCC patients with intrahepatic metastasis, major portal vein invasion, vascular invasion and/or an alpha-fetoprotein (AFP) level > 300 ng/ml.\nCONCLUSIONS: Contributing to an advanced tumor stage, intrahepatic metastasis, vascular invasion and AFP level elevation, RAD51AP1 upregulation was significantly associated with OS and DFS in HCC patients.", "claims": [{"id": "claim-method", "statement": "The Kaplan-Meier method with the log-rank test was used to compare OS and DFS between groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33269607", "locator": "sections[8] \"Statistical Analysis\" paragraph 2", "quote": "The Kaplan-Meier method with the log-rank test was used to compare OS and DFS between groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "To compare the RAD51AP1 expression levels in serum and tissues among patients with different stages of liver diseases, including HCC, and healthy candidates, GEO (https://www.ncbi.nlm.nih.gov/geo/) datasets including GSE84044,21 GSE17548,22 GSE45436,23 GSE55092,24 GSE101685, GSE4951525 and GSE3637626 were included in this analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33269607", "locator": "sections[4] \"Microarray Data\" paragraph 2", "quote": "To compare the RAD51AP1 expression levels in serum and tissues among patients with different stages of liver diseases, including HCC, and healthy candidates, GEO (https://www.ncbi.nlm.nih.gov/geo/) datasets including GSE84044,21 GSE17548,22 GSE45436,23 GSE55092,24 GSE101685, GSE4951525 and GSE3637626 were included in this analysis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:33269607"], "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. 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(8.9)", "37 (20.4)", ""], ["2", "80 (44.4)", "91 (50.3)", ""], ["3", "76 (42.2)", "45 (24.9)", ""], ["4", "7 (3.9)", "4 (2.2)", ""], ["AFP, n (%)", "", "", ""], ["> 200 ng/ml", "119 (66.1)", "67 (37.0)", "<0.001"], ["> 300 ng/ml", "114 (63.3)", "62 (34.3)", "<0.001"], ["> 400 ng/ml", "114 (63.3)", "61 (33.7)", "<0.001"], ["Platelet, mean ± SD, 103/mm3", "219.5 ± 8.7", "217.3 ± 7.7", "0.845"], ["Bilirubin, mean ± SD, mg/dl", "0.9 ± 0.1", "1.0 ± 0.2", "0.406"], ["Creatinine, mean ± SD, mg/dl", "1.9 ± 0.7", "3.6 ± 1.2", "0.228"], ["New tumor event after initial treatment, n (%)", "50 (27.8)", "43 (23.8)", "0.298"], ["Hepatic inflammation of adjacent tissue, n (%)", "", "", "0.636"], ["None", "51 (28.3)", "63 (34.8)", ""], ["Mild", "48 (26.7)", "49 (27.1)", ""], ["Severe", "7 (3.9)", "11 (6.1)", ""], ["Ishak stage, n (%)", "", "", "0.178"], ["None", "25 (13.9)", "47 (26.0)", ""], ["Portal fibrosis", "14 (7.8)", "17 (9.4)", ""], ["Fibrosis speta", "15 (8.3)", "13 (7.2)", ""], ["Nodular formation/cirrhosis", "40 (22.2)", "39 (21.5)", ""], ["Child-pugh classification, n (%)", "", "", "0.726"], ["A", "118 (65.6)", "115 (63.5)", ""], ["B and C", "12 (6.7)", "10 (5.5)", ""], ["Vascular invasion", "", "", "0.858"], ["None", "116 (64.4)", "105 (58.0)", ""], ["Macro and micro", "54 (30.0)", "51 (28.2)", ""], ["AJCC stage, n (%)", "", "", "<0.001"], ["I", "21 (11.7)", "0 (0)", ""], ["II", "74 (41.1)", "93 (51.4)", ""], ["III", "42 (23.3)", "40 (22.1)", ""], ["IV", "53 (29.4)", "35 (19.3)", ""], ["Risk factors, n (%)", "", "", "0.174"], ["None", "91 (50.6)", "80 (44.2)", ""], ["Alcohol assumption", "48 (26.7)", "57 (31.5)", ""], ["Viral hepatitis", "62 (34.4)", "44 (24.3)", ""], ["Estimated mean follow-up, months, mean ± SD†", "35.3 ± 2.7", "41.4 ± 2.7", "0.136"], ["Deceased, n (%)", "57 (31.5)", "72 (40)", "0.092"], ["OS months, mean ± SD", "30.6 ± 1.9", "22.7 ± 1.6", "0.002"]], "row_count": 54, "column_count": 4, "numeric_cells": 121, "header_rows": 1, "locator": "section[11]/table-wrap[1]#table1-1073274820977149"}}, {"id": "asset:table:pmid:33269607:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:42b213fa1810c240c4a9e5130703f73bb6181ed77126c4f2a12d455f8b688207", "bytes": 1495, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[2]#table2-1073274820977149", "version": null, "note": "Univariate and Multivariate Logistic Regression Models for Identifying Parameters Associated With RAD51AP1.#", "structure": {"pmcid": "PMC8480365", "section_index": 11, "section_title": "RAD51AP1 and HCC Survival", "row_count": 22, "column_count": 5}, "table": {"label": "Table 2.", "caption": "Univariate and Multivariate Logistic Regression Models for Identifying Parameters Associated With RAD51AP1.#", "rows": [["Variables", "Univariate", "p value", "Multivariate", "p value"], ["OR (95%CI)", "OR (95%CI)"], ["Race", "", "", "", ""], ["Asian", "Reference", "-", "Reference", "-"], ["White", "0.55 (0.36-0.86)", "0.008", "1.97 (0.87-4.48)", "0.106"], ["Others", "0.77 (0.3-2.01)", "0.597", "2.06 (0.46-9.28)", "0.347"], ["Grade", "", "", "", ""], ["I", "Reference", "-", "Reference", "-"], ["II", "2.12 (1.12-4.02)", "0.021", "4.15 (1.07-16.07)", "0.04"], ["III-IV", "4.09 (2.1-7.96)", "< 0.001", "5.75 (1.42-23.23)", "0.014"], ["AJCC staging", "", "", "", ""], ["1", "Reference", "-", "Reference", "-"], ["2", "1.32 (0.78-2.24)", "0.305", "0.67 (0.29-1.52)", "0.334"], ["3-4", "1.9 (1.13-3.22)", "0.016", "0.76 (0.3-1.89)", "0.55"], ["AFP > 200 ng/ml, yes vs. no", "2.03 (1.34-3.1)", "0.001", "1.53 (0.73-3.21)", "0.264"], ["Ishak stage", "", "", "", ""], ["None", "Reference", "-", "Reference", "-"], ["Portal fibrosis", "1.55 (0.66-3.65)", "0.318", "1.45 (0.51-4.08)", "0.486"], ["Fibrosis speta", "2.17 (0.89-5.27)", "0.087", "1.54 (0.49-4.83)", "0.457"], ["Nodular formation/cirrhosis", "1.93 (1.0-3.71)", "0.05", "2.45 (0.95-5.33)", "0.066"], ["Family history of cancer, yes vs. no", "0.49 (0.3-0.79)", "0.003", "0.58 (0.28-1.21)", "0.148"], ["Age, per increase 1 year", "0.98 (0.97-1.0)", "0.031", "0.99 (0.97-1.02)", "0.612"]], "row_count": 22, "column_count": 5, "numeric_cells": 55, "header_rows": 2, "locator": "section[11]/table-wrap[2]#table2-1073274820977149"}}], "gaps": ["asset:data:geo:GSE101685 not downloaded", "asset:data:geo:GSE101685 licence not read", "asset:data:geo:GSE17548 not downloaded", "asset:data:geo:GSE17548 licence not read", "asset:data:geo:GSE36376 not downloaded", "asset:data:geo:GSE36376 licence not read", "asset:data:geo:GSE45436 not downloaded", "asset:data:geo:GSE45436 licence not read", "asset:data:geo:GSE49515 not downloaded", "asset:data:geo:GSE49515 licence not read", "asset:data:geo:GSE55092 not downloaded", "asset:data:geo:GSE55092 licence not read", "asset:data:geo:GSE84044 not downloaded", "asset:data:geo:GSE84044 licence not read"]}, 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