Abnormal Expression and Prognostic Significance of Bone Morphogenetic Proteins and Their Receptors in Lung Adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34036102", "kind": "science-record", "revision": 7, "content_hash": "sha256:e72f723f676adff31729704ee220383aab034bfb815445ca9a51f4d404fb87f8", "created_at": "2026-11-01T15:41:36Z", "updated_at": "2026-11-01T22:03:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Abnormal Expression and Prognostic Significance of Bone Morphogenetic Proteins and Their Receptors in Lung Adenocarcinoma.", "doi": "10.1155/2021/6663990", "pmid": "34036102", "authors": ["Zhixiao Xu", "Chengshui Chen"], "journal": "BioMed research international", "year": 2021, "abstract": "BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most life-threatening malignancies. The crucial role of bone morphogenetic protein (BMP)/BMP receptors reveals the significance of exploring BMP protein-related prognostic predictors in LUAD.\nMETHODS: The mRNA expression of BMPs/BMP receptors was investigated in LUAD and normal lung tissues. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed, and the prognostic values were assessed by Kaplan-Meier Plotter. Univariate and multivariate Cox regression analyses were executed to ascertain the correlation between overall survival (OS) and the mRNA expression of BMPs/BMP receptors. The receiver operating characteristic (ROC) curves were implemented to evaluate the predictive power of the prognostic model. Then, the prognostic model was validated in the GEO cohort. Furthermore, a nomogram comprising the prognostic model was established.\nRESULTS: The mRNA expression of BMP2/5/6/R2, ACVRL1, and TGFBR2/3 was lower in LUAD tissues than in normal lung tissues. High expression of BMP2/4/5/R1A/R2, ACVR1/2A/L1, and TGFBR1/3 was associated with better OS, while BMP7 and ACVR1C/2B were associated with poorer OS. Three genes (BMP5, BMP7, and ACVR2A) were screened by univariate and multivariate Cox regression analyses to develop the prognostic model in TCGA. Significantly better survival was observed in LUAD patients with a low-risk score than those with a high-risk score. The ROC curves confirmed the good performance of the prognostic model, then, the prognostic model was validated in the GSE31210 dataset. A nomogram was constructed (AUCs>0.7). And hub genes were further evaluated, including gene set enrichment analysis and immune cell infiltration.\nCONCLUSIONS: BMP5, BMP7, and ACVR2A are potential therapeutic targets in LUAD. The three-gene prognostic model and the nomogram are reliable tools for predicting the OS of LUAD patients.", "claims": [{"id": "claim-method", "statement": "The online cancer database ONCOMINE (https://www.oncomine.org/) was beneficial to data mining of the transcriptional expression of BMPs/BMP receptors in 20 types of cancer. The student's t-test was used to assess whether there was a significant difference between the transcriptional expression of BMPs/BMP receptors in LUAD samples and those in normal lung samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34036102", "locator": "sections[3] \"2.1. Data-Mining Analysis by ONCOMINE Database\" paragraph 2", "quote": "The online cancer database ONCOMINE (https://www.oncomine.org/) was beneficial to data mining of the transcriptional expression of BMPs/BMP receptors in 20 types of cancer. The student's t-test was used to assess whether there was a significant difference between the transcriptional expression of BMPs/BMP receptors in LUAD samples and those in normal lung samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data sets analyzed during this study are publicly available databases, such as The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) dataset.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34036102", "locator": "sections[23] \"Data Availability\" paragraph 2", "quote": "The data sets analyzed during this study are publicly available databases, such as The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) dataset."}], "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:34036102"], "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:GSE31210"], "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:GSE31210"], "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:34036102", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/6663990", 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Transcriptional Levels of BMPs/BMP Receptors in LUAD Patients", "row_count": 30, "column_count": 5}, "table": {"label": "Table 1", "caption": "Differential expression of BMPs/BMP receptors in lung adenocarcinoma and normal lung tissue from the ONCOMINE database.", "rows": [["", "Fold change", "P value", "t-test", "Ref"], ["BMP2", "-10.392", "2.32E-07", "-6.654", "Bhattacharjee et al. [13]"], ["", "-2.455", "1.48E-08", "-6.567", "Su et al. [14]"], ["", "-2.539", "1.11E-14", "-8.858", "Landi et al. [15]"], ["", "-2.621", "4.01E-05", "-4.433", "Stearman et al. [16]"], ["", "-4.144", "2.05E-11", "-7.955", "Hou et al. [17]"], ["BMP5", "-6.923", "5.58E-08", "-6.680", "Beer et al. [18]"], ["", "-2.717", "2.50E-12", "-9.058", "Okayama et al. [19]"], ["", "-2.898", "5.07E-06", "-5.034", "Su et al. [14]"], ["", "-3.267", "7.37E-12", "-8.133", "Hou et al. [17]"], ["BMP6", "-2.544", "2.69E-10", "-9.409", "Okayama et al. [19]"], ["BMPR2", "-2.281", "5.66E-17", "-10.377", "Hou et al. 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[18]"], ["", "-6.330", "3.34E-20", "-12.985", "Hou et al. [17]"], ["", "-6.154", "6.78E-08", "-7.451", "Stearman et al. [16]"]], "row_count": 30, "column_count": 5, "numeric_cells": 116, "header_rows": 1, "locator": "section[12]/table-wrap[1]#tab1"}}, {"id": "asset:table:pmid:34036102:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d1173048a1167518e18019ba1a5fe6894e823730c0145b37cf637aab68a9a8da", "bytes": 1455, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#tab2", "version": null, "note": "Association of BMPs/BMP receptors expression with prognosis in LUAD patients revealed by Kaplan-Meier Plotter.", "structure": {"pmcid": "PMC8123996", "section_index": 15, "section_title": "3.4. The Prognostic Significance of BMPs/BMP Receptors in LUAD Patients", "row_count": 19, "column_count": 6}, "table": {"label": "Table 2", "caption": "Association of BMPs/BMP receptors expression with prognosis in LUAD patients revealed by Kaplan-Meier Plotter.", "rows": [["Name", "Cut-off value (counts)", "Range (counts)", "P value", "HR", "No. patients"], ["BMP2", "337", "5–7330", "0.0002", "0.64 (0.51-0.81)", "719"], ["BMP3", "49", "1–1053", "0.1001", "0.82 (0.65-1.04)", "719"], ["BMP4", "26", "2 –5308", "0.0239", "0.76 (0.60-0.96)", "719"], ["BMP5", "86", "0–4234", "6.90E-09", "0.50 (0.39-0.63)", "719"], ["BMP6", "185", "4–8180", "0.9815", "1.00 (0.79-1.26)", "719"], ["BMP7", "156", "1–3030", "0.2600", "1.17 (0.89-1.54)", "719"], ["BMPR1A", "370", "6–1789", "1.60E-08", "0.50 (0.39-0.64)", "719"], ["BMPR1B", "42", "-1–5621", "0.2820", "0.85 (0.62-1.15)", "672"], ["BMPR2", "752", "-1–9643", "0.0444", "0.75 (0.56-0.99)", "672"], ["ACVR1", "1283", "138–4666", "1.20E-07", "0.54 (0.42-0.68)", "719"], ["ACVR1B", "307", "5–2312", "0.0015", "1.45 (1.15-1.83)", "719"], ["ACVR1C", "50", "-1–2919", "0.4622", "1.11 (0.85-1.44)", "672"], ["ACVR2A", "168", "-1–1710", "0.0007", "0.64 (0.49-0.83)", "672"], ["ACVR2B", "8", "-1–382", "0.7751", "1.04 (0.80-1.35)", "672"], ["ACVRL1", "133", "-1–3761", "0.0158", "0.64 (0.44-0.92)", "672"], ["TGFBR1", "1212", "-1–13618", "0.1066", "0.80 (0.61-1.05)", "672"], ["TGFBR2", "41", "1–658", "0.0377", "1.28 (1.01-1.63)", "719"], ["TGFBR3", "268", "-1–12138", "0.0003", "0.61 (0.47-0.80)", "672"]], "row_count": 19, "column_count": 6, "numeric_cells": 90, "header_rows": 1, "locator": "section[15]/table-wrap[1]#tab2"}}], "gaps": ["asset:data:geo:GSE31210 not downloaded", "asset:data:geo:GSE31210 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The online cancer database ONCOMINE (https://www.oncomine.org/) was beneficial to data mining of the transcriptional expression of BMPs/BMP receptors in 20 types of cancer. 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