Macrophage-Related SPP1 as a Potential Biomarker for Early Lymph Node Metastasis in Lung Adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34646827", "kind": "science-record", "revision": 4, "content_hash": "sha256:83b8deb6538fe3fceeda8e881819fa3b7a5cc3b3c14368347d62c6141bbb1c9a", "created_at": "2026-11-01T17:36:18Z", "updated_at": "2026-11-01T22:04:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Macrophage-Related SPP1 as a Potential Biomarker for Early Lymph Node Metastasis in Lung Adenocarcinoma.", "doi": "10.3389/fcell.2021.739358", "pmid": "34646827", "authors": ["Bo Dong", "Chunli Wu", "Lan Huang", "Yu Qi"], "journal": "Frontiers in cell and developmental biology", "year": 2021, "abstract": "Lymph node metastasis is a major factor that affects prognosis in patients with lung adenocarcinoma (LUAD). In some cases, lymph node metastasis has already occurred when the primary tumors are still small (i.e., early T stages), however, relevant studies on early lymph node metastasis are limited, and effective biomarkers remain lacking. This study aimed to explore new molecular biomarker for early lymph node metastasis in LUAD using transcriptome sequencing and experimental validation. Here, we performed transcriptome sequencing on tissues from 16 matched patients with Stage-T1 LUAD (eight cases of lymph node metastasis and eight cases of non-metastasis), and verified the transcriptome profiles in TCGA, GSE68465, and GSE43580 cohorts. With the bioinformatics analysis, we identified a higher abundance of M0 macrophages in the metastatic group using the CIBERSORT algorithm and immunohistochemistry (IHC) analysis and the enrichment of the epithelial-mesenchymal transition (EMT) pathway was identified in patients with higher M0 infiltration levels. Subsequently, the EMT hallmark gene SPP1, encoding secreted phosphoprotein 1 (SPP1), was identified to be significantly correlated with macrophage infiltration and M2 polarization, and was determined to be a key risk indicator for early lymph node metastasis. Notably, SPP1 in the blood, as detected by enzyme-linked immunosorbent assay (ELISA) showed a superior predictive capability for early lymph node metastasis [area under the curve (AUC) = 0.74]. Furthermore, a long non-coding RNA (lncRNA, AC037441), negatively correlated with SPP1 and macrophage infiltration, had also been identified and validated to be involved in the regulation of early lymph node metastasis. In conclusion, we revealed the potential role of macrophages in lymph node metastasis and identified the macrophage-related gene SPP1 as a potential biomarker for early lymph node metastasis in LUAD.", "claims": [{"id": "claim-method", "statement": "The relative proportion of 22 immune cells were determined for Stage-T1 LUAD and adjacent lung samples using the CIBERSORT algorithm1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34646827", "locator": "sections[4] \"Bioinformatics Analysis\" paragraph 2", "quote": "The relative proportion of 22 immune cells were determined for Stage-T1 LUAD and adjacent lung samples using the CIBERSORT algorithm1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Transcript sequencing data and clinical information for the 31 patient samples analyzed in this study can be found in the Supplementary Material. In addition, publicly available datasets were analyzed in this study, which can be found at TCGA (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga) and GEO omnibus (https://www.ncbi.nlm.nih.gov/geo/) (GSE68465 and GSE43580).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34646827", "locator": "sections[19] \"Data Availability Statement\" paragraph 2", "quote": "Transcript sequencing data and clinical information for the 31 patient samples analyzed in this study can be found in the Supplementary Material. In addition, publicly available datasets were analyzed in this study, which can be found at TCGA (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga) and GEO omnibus (https://www.ncbi.nlm.nih.gov/geo/) (GSE68465 and GSE43580)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "SPP1 detected in blood by ELISA showed a superior predictive capability for early lymph node metastasis, with an AUC of 0.74.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34646827", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Notably, SPP1 in the blood, as detected by enzyme-linked immunosorbent assay (ELISA) showed a superior predictive capability for early lymph node metastasis [area under the curve (AUC) = 0.74]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "SPP1 detected in blood by ELISA showed a superior predictive capability for early lymph node metastasis, with an AUC of 0.74.", "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:34646827"], "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:GSE43580"], "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:GSE43580"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34646827", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2021.739358", "sha256": "sha256:4ac278df12e81180bffe176bfb19dddaf6c42de4ab7be2051da1529caf794a4c", "bytes": 51022, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcell.2021.739358", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8502925", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE43580", "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=GSE43580", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE43580", "version": null, "note": "Transcript sequencing data and clinical information for the 31 patient samples analyzed in this study can be found in the Supplementary Material. 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