Secreted proteins MDK, WFDC2, and CXCL14 as candidate biomarkers for early diagnosis of lung adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36721112", "kind": "science-record", "revision": 3, "content_hash": "sha256:87bd0aa149227d6fa1219d307caa8be8c72bc55774e536d0033e56bdf5e53f4b", "created_at": "2026-11-01T19:01:17Z", "updated_at": "2026-11-01T22:08:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Secreted proteins MDK, WFDC2, and CXCL14 as candidate biomarkers for early diagnosis of lung adenocarcinoma.", "doi": "10.1186/s12885-023-10523-z", "pmid": "36721112", "authors": ["Junfeng Li", "Jianjie Li", "Huifeng Hao", "Fangliang Lu", "Jia Wang", "Menglei Ma", "Bo Jia", "Minglei Zhuo", "Jingjing Wang", "Yujia Chi", "Xiaoyu Zhai", "Yuyan Wang", "Meina Wu", "Tongtong An", "Jun Zhao", "Fan Yang", "Ziping Wang"], "journal": "BMC cancer", "year": 2023, "abstract": "BACKGROUND: Early diagnosis of lung adenocarcinoma (LUAD), one of the most common types of lung cancer, is very important to improve the prognosis of patients. The current methods can't meet the requirements of early diagnosis. There is a pressing need to identify novel diagnostic biomarkers. Secretory proteins are the richest source for biomarker research. This study aimed to identify candidate secretory protein biomarkers for early diagnosis of LUAD by integrated bioinformatics analysis and clinical validation.\nMETHODS: Differentially expressed genes (DEGs) of GSE31210, gene expression data of early stage of LUAD, were analyzed by GEO2R. Upregulated DEGs predicted to encode secreted proteins were obtained by taking the intersection of the DEGs list with the list of genes encoding secreted proteins predicted by the majority decision-based method (MDSEC). The expressions of the identified secreted proteins in the lung tissues of early-stage LUAD patients were further compared with the healthy control group in mRNA and protein levels by using the UALCAN database (TCGA and CPTAC). The selected proteins expressed in plasma were further validated by using Luminex technology. The diagnostic value of the screened proteins was evaluated by receiver operating characteristic (ROC) analysis. Cell counting kit-8 assay was carried out to investigate the proliferative effects of these screened proteins.\nRESULTS: A total of 2183 DEGs, including 1240 downregulated genes and 943 upregulated genes, were identified in the GSE31210. Of the upregulated genes, 199 genes were predicted to encode secreted proteins. After analysis using the UALCAN database, 16 molecules were selected for further clinical validation. Plasma concentrations of three proteins, Midkine (MDK), WAP four-disulfide core domain 2 (WFDC2), and C-X-C motif chemokine ligand 14 (CXCL14), were significantly higher in LUAD patients than in healthy donors. The area under the curve values was 0.944, 0.881, and 0.809 for MDK, WFDC2, and CXCL14, 0.962 when combined them. Overexpression of the three proteins enhanced the proliferation activity of A549 cells.\nCONCLUSIONS: MDK, WFDC2, and CXCL14 were identified as candidate diagnostic biomarkers for early-stage LUAD and might also play vital roles in tumorigenesis.", "claims": [{"id": "claim-method", "statement": "The diagnostic performance of each candidate biomarker or their combination was assessed by the ROC analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36721112", "locator": "sections[10] \"Receiver operating characteristic (ROC) analysis\" paragraph 2", "quote": "The diagnostic performance of each candidate biomarker or their combination was assessed by the ROC analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data on plasma protein concentrations of the 26 stage I LUAD patients and 11 health donors are available from the authors upon reasonable request. All other data analyzed in this study were obtained from the GEO dataset GSE31210 and the UALCAN database (TCGA and CPTAC) as above-mentioned.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36721112", "locator": "sections[29] \"Availability of data and materials\" paragraph 2", "quote": "Data on plasma protein concentrations of the 26 stage I LUAD patients and 11 health donors are available from the authors upon reasonable request. All other data analyzed in this study were obtained from the GEO dataset GSE31210 and the UALCAN database (TCGA and CPTAC) as above-mentioned."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The area under the curve values was 0.944, 0.881, and 0.809 for MDK, WFDC2, and CXCL14, 0.962 when combined them.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36721112", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The area under the curve values was 0.944, 0.881, and 0.809 for MDK, WFDC2, and CXCL14, 0.962 when combined them."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The area under the curve values was 0.944, 0.881, and 0.809 for MDK, WFDC2, and CXCL14, 0.962 when combined them.", "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:36721112"], "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": "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:GSE31210"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36721112", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12885-023-10523-z", "sha256": "sha256:c314cad8e6f09a593123591ba1653cd7537455819fd2988621eee0f2d1a8b7a9", "bytes": 39365, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12885-023-10523-z", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9887767", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE31210", "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=GSE31210", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31210", "version": null, "note": "Data on plasma protein concentrations of the 26 stage I LUAD patients and 11 health donors are available from the authors upon reasonable request. All other data analyzed in this study were obtained from the GEO dataset GSE31210 and the UALCAN database (TCGA and CPTAC) as above-mentioned.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data on plasma protein concentrations of the 26 stage I LUAD patients and 11 health donors are available from the authors upon reasonable request. 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CONCLUSIONS: MDK, WFDC2, and CXCL14 w", "els of MDK, WFDC2, and CXCL14 expressions in A549 cells using GAPDH as an internal control."], "order_basis": "paper_text_order:2187", "id": "assay:2"}, {"role": "analysis", "definition_id": "diagnostic_evaluation", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["ROC analysis"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}