OPCML Methylation and the Risk of Ovarian Cancer: A Meta and Bioinformatics Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33777925", "kind": "science-record", "revision": 7, "content_hash": "sha256:3d1a0c874fdc2ca51fbae27b68a9838b5aa573554de4d3926f0d71be0d276864", "created_at": "2026-11-01T15:41:30Z", "updated_at": "2026-11-01T22:03:26Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "OPCML Methylation and the Risk of Ovarian Cancer: A Meta and Bioinformatics Analysis.", "doi": "10.3389/fcell.2021.570898", "pmid": "33777925", "authors": ["Yang Shao", "Jing Kong", "Hanzi Xu", "Xiaoli Wu", "YuePeng Cao", "Weijian Li", "Jing Han", "Dake Li", "Kaipeng Xie", "Jiangping Wu"], "journal": "Frontiers in cell and developmental biology", "year": 2021, "abstract": "Background: The association of opioid binding protein cell adhesion molecule-like (OPCML) gene methylation with ovarian cancer risk remains unclear. Methods: We identified eligible studies by searching the PubMed, Web of Science, ScienceDirect, and Wanfang databases. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to determine the association of OPCML methylation with ovarian cancer risk. Meta-regression and subgroup analysis were used to assess the sources of heterogeneity. Additionally, we analyzed the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets to validate our findings. Results: Our study included 476 ovarian cancer patients and 385 controls from eight eligible studies. The pooled OR was 33.47 (95% CI = 12.43-90.16) in the cancer group vs. the control group under the random-effects model. The association was still significant in subgroups according to sample type, control type, methods, and sample sizes (all P < 0.05). Sensitivity analysis showed that the finding was robust. No publication bias was observed in Begg's (P = 0.458) and Egger's tests (P = 0.261). We further found that OPCML methylation was related to III/IV (OR = 4.20, 95% CI = 1.59-11.14) and poorly differentiated grade (OR = 4.37; 95% CI = 1.14-16.78). Based on GSE146552 and GSE155760, we validated that three CpG sites (cg16639665, cg23236270, cg15964611) in OPCML promoter region were significantly higher in cancer tissues compared to normal tissues. However, we did not observe the associations of OPCML methylation with clinicopathological parameters and overall survival based on TCGA ovarian cancer data. Conclusion: Our findings support that OPCML methylation is associated with an increased risk of ovarian cancer.", "claims": [{"id": "claim-method", "statement": "Because of significant heterogeneity among the included studies, a random-effects model was used to evaluate the effect size (P < 0.01; I2 = 65%; Figure 2).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33777925", "locator": "sections[10] \"Relationship Between OPCML Methylation and Ovarian Cancer Risk\" paragraph 2", "quote": "Because of significant heterogeneity among the included studies, a random-effects model was used to evaluate the effect size (P < 0.01; I2 = 65%; Figure 2)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33777925", "locator": "sections[17] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."}], "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:33777925"], "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:GSE146552"], "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:GSE146552"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33777925", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2021.570898", "sha256": 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the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4711626", "GSM4711627", "GSM4711628", "GSM4711629", "GSM4711630", "GSM4711631", "GSM4711632", "GSM4711633", "GSM4711634", "GSM4711635", "GSM4711636", "GSM4711637", "GSM4711638", "GSM4711639", "GSM4711640", "GSM4711641", "GSM4711642", "GSM4711643", "GSM4711644", "GSM4711645", "GSM4711646", "GSM4711647", "GSM4711648", "GSM4711649", "GSM4711650", "GSM4711651", "GSM4711652", "GSM4711653", "GSM4711654", "GSM4711655", "GSM4711656", "GSM4711657", "GSM4711658", "GSM4711659", "GSM4711660", "GSM4711661", "GSM4711662", "GSM4711663", "GSM4711664", "GSM4711665", "GSM4711666", "GSM4711667", "GSM4711668", "GSM4711669", "GSM4711670", "GSM4711671", "GSM4711672", "GSM4711673", "GSM4711674", "GSM4711679", "GSM4711680", "GSM4711681", "GSM4711682", "GSM4711683", "GSM4711684", "GSM4711685", "GSM4711686", "GSM4711687", 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"table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0a9813f89917377401b43e622eaa67fff5b85200afe681ab97cbbc8fc213ec5e", "bytes": 2700, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#T1", "version": null, "note": "Characteristics of included studies.", "structure": {"pmcid": "PMC7990783", "section_index": 9, "section_title": "Study Characteristics", "row_count": 13, "column_count": 11}, "table": {"label": "Table 1", "caption": "Characteristics of included studies.", "rows": [["References", "Country", "Age (mean or median)", "Cancer group", "Control group", "Sample type", "Control type", "Method", "Methylation frequency of OPCML associated with other clinicopathological parameters"], ["", "", "", "M", "U", "M", "U", "", "", "", ""], ["Wang et al. (2015)", "China", "Cancer, 54.06 years. Benign, 33.95 years. Healthy, 46.17 years.", "64", "7", "11a", "112a", "Serum", "BOT&NT", "MSP", "FIGO stage: I/II (33/39), III/IV (30/32)."], ["Xing et al. (2015)", "China", "NR", "27", "8", "2", "9", "Tissues", "NT", "CCP-based FRET", "Age: <60 years (23/28), ≥60 years (4/7). FIGO stage: I/II (5/11), III/IV (22/24). Histological type: serous (22/26), others (5/9)b. Grade of differentiationc: High-grade serous (19/21), others (8/14) Ascites: positive (21/24), Negative (6/11). CA125: >200 U/mL (21/25), <200 U/mL (6/10)"], ["Zhou et al. (2014a)", "China", "Cancer and normal, 50 years.", "39", "6", "0d", "40d", "Tissues", "NT", "MSRE-PCR", "Tissues FIGO stage: I/II (5/10), III/IV (34/35). Histological type: serous (18/20), others (21/25)e. Tumor differentiation: Well and moderately differentiated (10/16), Poorly differentiated (29/29)."], ["", "", "Healthy, 50 years.", "36", "9", "0d", "20d", "Serum", "NT", "MSRE-PCR", "Serum FIGO stage: I/II (5/10), III/IV (31/35). Histological type: serous (17/20), others (19/25)e. Tumor differentiation: Well and moderately differentiated (9/16), Poorly differentiated (27/29)."], ["Zhou et al. (2014b)", "China", "Cancer, 54 years. Benign, 53 years. Normal, 54 years.", "80", "22", "0f", "30f", "Tissues", "NT", "MSP", "Age: <55 years (39/54), ≥55 years (41/48). Pathological stage*: I/II (31/44), III/IV (49/58). Histological typeb: serous (42/57), others (38/45)."], ["", "", "", "–", "–", "28f", "57f", "Tissues", "BOT", "MSP", ""], ["Czekierdowski et al. (2006)", "Poland", "NRg", "20", "23", "0", "4", "Tissues", "NT", "MSP", "FIGO stage: I/II (4/5), III/IV (16/38). Histological type: serous (8/15), others (12/28)h. Histological Grading: G1+G2 (11/20), G3 (9/23)k"], ["Zhang et al. (2006)", "China", "Cancer, 51.5 years. Benign, 39.0 years. Normal, 46.5 years.", "32", "40", "0", "20", "Tissues", "NT", "Restriction enzyme cut", ""], ["", "", "", "", "", "0", "17", "Tissues", "BOT", "Restriction enzyme cut", ""], ["Liu et al. (2008)i", "China", "Cancer, 53.8 years. Normal, 53.2 years.", "30", "33", "0", "20", "Tissues", "NT", "MSP", "FIGO stage: I/II (2/22), III/IV (16/41). Histological type: serous (20/34), others (10/29)j. Grading: Well and Moderately differentiated (6/36), Poorly differentiated (12/27)"], ["", "", "", "", "", "2", "13", "Tissues", "AT", "", ""]], "row_count": 13, "column_count": 11, "numeric_cells": 58, "header_rows": 2, "locator": "section[9]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33777925:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:68b3c7bf053ee53447e59de8bceb739e648e7a8d8d69a108d826c7df651fb16f", "bytes": 543, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#T2", "version": null, "note": "Meta-regression analysis.", "structure": {"pmcid": "PMC7990783", "section_index": 11, "section_title": "Meta-Regression and Subgroup Analysis", "row_count": 7, "column_count": 4}, "table": {"label": "Table 2", "caption": "Meta-regression analysis.", "rows": [["Heterogeneity sources", "Coefficient", "95% CI", "P"], ["Publication year", "0.814", "(−0.751, 2.380)", "0.308"], ["Country", "10.538", "(−9.721, 30.795)", "0.308"], ["Sample type", "−0.716", "(−3.370, 1.939)", "0.597"], ["Control type", "4.851", "(−4.042,13.744)", "0.285"], ["Method", "3.748", "(−1.419, 8.916)", "0.155"], ["Sample size", "−0.001", "(−0.020, 0.018)", "0.889"]], "row_count": 7, "column_count": 4, "numeric_cells": 19, "header_rows": 1, "locator": "section[11]/table-wrap[1]#T2"}}, {"id": "asset:table:pmid:33777925:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f65bb819a4abd8a52c7f694f833e66904705bfbe9c738691e1b639b2eadc0551", "bytes": 1760, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[2]#T3", "version": null, "note": "Subgroup analysis of associations between OPCML methylation and ovarian cancer risk.", "structure": {"pmcid": "PMC7990783", "section_index": 11, "section_title": "Meta-Regression and Subgroup Analysis", "row_count": 19, "column_count": 10}, "table": {"label": "Table 3", "caption": "Subgroup analysis of associations between OPCML methylation and ovarian cancer risk.", "rows": [["Group", "Studies", "Case", "Control", "Fixed effects model", "Random effects model", "Heterogeneity"], ["", "n", "M", "U", "M", "U", "OR (95% CI)", "OR (95% CI)", "I2 (%)", "P"], ["Country", "", "", "", "", "", "", "", "", ""], ["China", "7", "308", "125", "43", "338", "27.47 (17.52, 43.08)", "38.17 (13.21, 110.28)", "70", "<0.01"], ["Poland", "1", "20", "23", "0", "4", "7.85 (0.40, 154.75)", "7.85 (0.40, 154.75)", "–", "–"], ["Sample type", "", "", "", "", "", "", "", "", ""], ["Serum", "2", "100", "16", "11", "132", "102.86 (39.37, 268.74)", "98.42 (38.37, 252.45)", "0", "0.73"], ["Tissues", "6", "228", "132", "32", "210", "18.22 (10.93, 30.36)", "19.13 (7.71, 47.44)", "39", "0.15"], ["Control type", "", "", "", "", "", "", "", "", ""], ["NT", "4", "122", "46", "2", "73", "52.77 (16.92, 164.55)", "47.94 (7.38, 311.27)", "53", "0.09"], ["NT&BOT", "3", "176", "69", "39", "236", "23.41 (13.96, 39.25)", "35.50 (6.38, 197.47)", "84", "<0.01"], ["AT&NT", "1", "30", "33", "2", "33", "15.00 (3.31, 67.93)", "15.00 (3.31, 67.93)", "–", "–"], ["Methods", "", "", "", "", "", "", "", "", ""], ["MSP", "4", "194", "85", "41", "236", "19.52 (11.94, 31.92)", "21.78 (6.10, 77.79)", "76", "<0.01"], ["CCP-based FRET", "1", "27", "8", "2", "9", "15.19 (2.71, 85.10)", "15.19 (2.71, 85.10)", "–", "–"], ["Restriction enzyme related methods", "3", "107", "55", "0", "97", "139.45 (24.06, 808.26)", "163.86 (31.13, 862.61)", "0", "0.59"], ["Sample size", "", "", "", "", "", "", "", "", ""], ["<100", "5", "152", "79", "4", "106", "34.19 (14.11, 82.86)", "32.63 (8.42, 126.53)", "45", "0.12"], ["≥100", "3", "176", "69", "39", "236", "23.41 (13.96, 39.25)", "35.50 (6.38, 197.47)", "84", "<0.01"]], "row_count": 19, "column_count": 10, "numeric_cells": 106, "header_rows": 2, "locator": "section[11]/table-wrap[2]#T3"}}, {"id": "asset:table:pmid:33777925:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f8db2b4102f1dbee7d8183b7dbd9be3fbf29b7138ed3a39fdfb7ee259cfb50cd", "bytes": 6894, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#T4", "version": null, "note": "Consistently differential DNA methylated sites (P < 0.05 and the same direction of logFC in both datasets) between ovarian cancer tissues and normal tissues based on GEO DNA methylation datasets.", "structure": {"pmcid": "PMC7990783", "section_index": 15, "section_title": "Validation of the Results in Multiple Public Databases", "row_count": 57, "column_count": 9}, "table": {"label": "Table 4", "caption": "Consistently differential DNA methylated sites (P < 0.05 and the same direction of logFC in both datasets) between ovarian cancer tissues and normal tissues based on GEO DNA methylation datasets.", "rows": [["ID", "chrom", "chromStart", "chromEnd", "GSE155760", "GSE146552", "Gene"], ["", "", "", "", "logFC", "P-value", "logFC", "P-value", ""], ["cg01875106", "chr11", "132287341", "132287343", "−0.6360", "1.050 × 10−12", "−0.2740", "1.500 × 10−4", "OPCML"], ["cg11500790", "chr11", "132321480", "132321482", "−0.5980", "1.400 × 10−7", "−0.3440", "8.150 × 10−5", "OPCML"], ["cg05806819", "chr11", "132432636", "132432638", "−0.0195", "3.980 × 10−2", "−0.0523", "3.340 × 10−2", "OPCML"], ["cg03784083", "chr11", "132513894", "132513896", "−0.4300", "4.610 × 10−4", "−0.2160", "4.350 × 10−3", "OPCML"], ["cg08080489", "chr11", "132526946", "132526948", "−0.5720", "6.510 × 10−8", "−0.2800", "1.240 × 10−4", "OPCML"], ["cg17242596", "chr11", "132527295", "132527297", "−0.6000", "3.930 × 10−8", "−0.3990", "1.650 × 10−5", "OPCML"], ["cg06967998", "chr11", "132527437", "132527439", "−0.6200", "1.490 × 10−7", "−0.3880", "2.850 × 10−5", 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