Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1) Are Associated with Progression and Prognosis of Esophageal Cancer as Identified by Integrated Expression Profiles Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32208405", "kind": "science-record", "revision": 8, "content_hash": "sha256:6e55e0fee62fe8ef539c0f3e6a972c36bb2b14b3f60d64d3ab5f1938806c77fb", "created_at": "2026-11-01T15:40:58Z", "updated_at": "2026-11-01T22:01:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1) Are Associated with Progression and Prognosis of Esophageal Cancer as Identified by Integrated Expression Profiles Analysis.", "doi": "10.12659/MSM.920355", "pmid": "32208405", "authors": ["Menglu Li", "Kaige Wang", "Yanhua Pang", "Hongpan Zhang", "Hao Peng", "Qi Shi", "Zhiyu Zhang", "Xiaobin Cui", "Feng Li"], "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2020, "abstract": "BACKGROUND Esophageal cancer is a malignant tumor with a complex pathogenesis and a poor 5-year survival rate, which encourages researchers to explore its molecular mechanisms deeper to improve the prognosis. MATERIAL AND METHODS DEGs were from 4 Gene Expression Omnibus (GEO) databases (GSE92396, GSE20347, GSE23400, and GSE45168) including 87 esophageal tumor samples and 84 normal samples. We performed Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Protein-Protein interaction (PPI) analysis, and GeneMANIA to identify the DEGs. Gene set enrichment analysis (GSEA) and Kaplan-Meier survival analyses were performed. RESULTS There was an overlapping subset consisting of 120 DEGs that was present in all esophageal tumor samples. The DEGs were enriched in extracellular matrix (ECM)-receptor interaction, as well as focal adhesion and transcriptional mis-regulation in cancer. The 2 most crucial regulatory pathways in esophageal cancer were the amebiasis pathway and the PI3K-Akt signaling pathway. Secreted phosphoprotein 1 (SPP1) and fibronectin 1 (FN1) were selected and verified in an independent cohort and samples using the TCGA and GTEx projects. Gene set enrichment analysis (GSEA) showed that proteasome and nucleotide excision repair were 2 most differentially enriched pathways in the SPP1 high-expression phenotype, and ECM-receptor interaction and focal adhesion in FN1 high-expression phenotype. Kaplan-Meier survival analysis showed that SPP1 and FN1 were significantly positively related to overall survival and had the potential to predict patient relapse. CONCLUSIONS Our analysis is the first to show that SPP1 and FN1 might work as biological markers of progression and prognosis in esophageal carcinoma (ESCA).", "claims": [{"id": "claim-method", "statement": "Comparisons of the 2 groups were made using the t test, or with non-parametric test when the overall distribution was unclear.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32208405", "locator": "sections[8] \"Statistical analysis\" paragraph 2", "quote": "Comparisons of the 2 groups were made using the t test, or with non-parametric test when the overall distribution was unclear."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Dataset GSE92396, analyzed with the GPL6244 platform ([HuGene-10-st] Affymetrix Human Gene 1.0 ST Array), consisted of 21 samples including 12 esophageal tumor tissues and 9 normal esophageal tissues.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32208405", "locator": "sections[3] \"Screening gene expression profile data\" paragraph 3", "quote": "Dataset GSE92396, analyzed with the GPL6244 platform ([HuGene-10-st] Affymetrix Human Gene 1.0 ST Array), consisted of 21 samples including 12 esophageal tumor tissues and 9 normal esophageal tissues."}], "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:32208405"], "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:GSE13898"], "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:GSE13898"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32208405", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.12659/MSM.920355", "sha256": 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"reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#t2-medscimonit-26-e920355", "version": null, "note": "KEGG pathway analysis of differentially expressed genes associated with esophageal cancer.", "structure": {"pmcid": "PMC7111131", "section_index": 11, "section_title": "Functional enrichment of differentially expressed genes", "row_count": 7, "column_count": 8}, "table": {"label": "Table 2", "caption": "KEGG pathway analysis of differentially expressed genes associated with esophageal cancer.", "rows": [["Category", "Term", "Count", "%", "P value", "Genes", "Fold Enrichment", "FDR"], ["KEGG_PATHWAY", "hsa05146: Amebiasis", "8", "6.67", "7.19E-06", "COL3A1, SERPINB2, SERPINB1, LAMC2, COL1A1, SERPINB13, COL5A2, FN1", "10.64", "8.11E-03"], ["KEGG_PATHWAY", "hsa04512: ECM-receptor interaction", "7", "5.83", "2.69E-05", "COL3A1, COL6A3, LAMC2, COL1A1, COL5A2, SPP1, FN1", "11.35", "3.03E-02"], ["KEGG_PATHWAY", "hsa04510: Focal adhesion", "7", 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"reader_status": "available", "identifier": "section[11]/table-wrap[2]#t3-medscimonit-26-e920355", "version": null, "note": "Gene ontology analysis of differentially expressed genes associated with esophageal cancer.", "structure": {"pmcid": "PMC7111131", "section_index": 11, "section_title": "Functional enrichment of differentially expressed genes", "row_count": 26, "column_count": 8}, "table": {"label": "Table 3", "caption": "Gene ontology analysis of differentially expressed genes associated with esophageal cancer.", "rows": [["Category", "Term", "Count", "%", "P value", "Genes", "Fold enrichment", "FDR"], ["GOTERM_BP_DIRECT", "GO: 0030198~ extracellular matrix organization", "16", "13.33", "3.95E-12", "PXDN, COL3A1, POSTN, SPINK5, COL5A2, BGN, ERO1A, SERPINE1, TGFBI, COL6A3, LAMC2, MFAP2, VCAN, COL1A1, SPP1, FN1", "12.02", "5.98E-09"], ["GOTERM_BP_DIRECT", "GO: 0030574~ collagen catabolic process", "9", "7.50", "1.06E-08", "MMP9, COL3A1, COL6A3, COL1A1, MMP3, COL5A2, MMP12, MMP1, MMP11", "20.71", "1.60E-05"], ["GOTERM_BP_DIRECT", "GO: 0022617~ extracellular matrix disassembly", "9", "7.50", "4.22E-08", "MMP9, LAMC2, MMP3, MMP12, MMP1, SPP1, MMP11, FN1, TIMP1", "17.44", "6.39E-05"], ["GOTERM_BP_DIRECT", "GO: 0007155~ cell adhesion", "17", "14.17", "7.28E-08", "PTPRK, SLURP1, POSTN, THY1, TNFAIP6, SORBS2, FAP, FAT1, COL6A3, TGFBI, LAMC2, VCAN, COL1A1, LOXL2, SPP1, FN1, CDH11", "5.46", "1.10E-04"], ["GOTERM_BP_DIRECT", "GO: 0030199~ collagen fibril organization", "6", "5.00", "6.06E-06", "COL3A1, COL1A1, LOXL2, SERPINH1, COL5A2, MMP11", "22.66", "9.18E-03"], ["GOTERM_BP_DIRECT", "GO: 0018149~ peptide cross-linking", "6", "5.00", "2.10E-05", "CRCT1, SPRR1A, COL3A1, TGM1, TGM3, FN1", "17.68", "3.18E-02"], ["GOTERM_BP_DIRECT", "GO: 0030336~ negative regulation of cell migration", "7", "5.83", "4.34E-05", "PTPRK, SLURP1, SULF1, SERPINE1, PTN, KANK1, THY1", "10.85", "6.57E-02"], ["GOTERM_BP_DIRECT", "GO: 0010951~ negative regulation of endopeptidase activity", "7", "5.83", "1.67E-04", "COL6A3, SERPINE1, SERPINB2, SERPINB1, SERPINB13, SERPINH1, TIMP1", "8.52", "2.52E-01"], ["GOTERM_BP_DIRECT", "GO: 0001501~ skeletal system development", "7", "5.83", "3.27E-04", "MMP9, COL3A1, POSTN, VCAN, COL1A1, COL5A2, CDH11", "7.53", "4.94E-01"], ["GOTERM_BP_DIRECT", "GO: 0006508~ proteolysis", "12", "10.00", "5.51E-04", "CLCA4, FAP, MMP9, TMPRSS11E, ENDOU, KLK12, MMP3, MMP12, PLAU, MMP1, MMP11, KLK13", "3.54", "8.31E-01"], ["GOTERM_BP_DIRECT", "GO: 0001525~ angiogenesis", "8", "6.67", "7.78E-04", "IL18, FAP, TGFBI, SERPINE1, RORA, ECM1, FN1, THY1", "5.28", "1.17E+00"], ["GOTERM_CC_DIRECT", "GO: 0005615~ extracellular space", "37", "30.83", "8.29E-14", "PXDN, SLURP1, MMP9, IL18, COL3A1, ENDOU, POSTN, MMP3, SERPINH1, TIMP1, FAP, COL6A3, TGFBI, SERPINE1, KLK12, PTN, SERPINB13, LOXL2, SPP1, KLK13, FN1, CRISP3, IL1RN, CST1, ECM1, ACPP, TNFAIP6, SULF1, NUCB2, SERPINB2, SERPINB1, LAMC2, VCAN, COL1A1, IGFBP3, PLAU, IL36A", "4.21", "9.93E-11"], ["GOTERM_CC_DIRECT", "GO: 0070062~ extracellular exosome", "53", "44.17", "1.05E-13", "PXDN, SLURP1, MMP9, IL18, CRABP2, SULT2B1, SPINK5, SLK, SERPINE1, TGFBI, KLK12, AHNAK, KLK13, CRISP3, ACADM, CLCA4, CRYAB, KRT13, GLTP, THY1, BGN, CLIC3, NUCB2, SERPINB1, PSCA, EPS8L1, ALDH9A1, ALOX12, CRNN, SERPINH1, TIMP1, KRT24, GPD1L, ADIRF, PPL, FAT1, TGM1, COL6A3, TGM3, SERPINB13, NDRG2, SCNN1B, TRIP10, FN1, SPP1, IL1RN, ECM1, UBL3, ACPP, IGFBP3, HPGD, PLAU, CDH11", "2.89", "1.25E-10"], ["GOTERM_CC_DIRECT", "GO: 0005578~ proteinaceous extracellular matrix", "17", "14.17", "1.86E-11", "ASPN, CRISP3, PXDN, MMP9, POSTN, MMP3, ECM1, COL5A2, MMP12, MMP1, TIMP1, MMP11, BGN, COL6A3, TGFBI, VCAN, FN1", "9.71", "2.23E-08"], ["GOTERM_CC_DIRECT", "GO: 0031012~ extracellular matrix", "16", "13.33", "8.17E-10", "ASPN, PXDN, COL3A1, POSTN, ECM1, COL5A2, MMP1, MMP11, BGN, SERPINE1, TGFBI, COL6A3, VCAN, COL1A1, LOXL2, FN1", "8.28", "9.78E-07"], ["GOTERM_CC_DIRECT", "GO: 0005576~ extracellular region", "31", "25.83", "8.14E-08", "SLURP1, MMP9, IL18, COL3A1, ENDOU, MMP3, SPINK5, MMP1, TIMP1, COL6A3, TGFBI, SERPINE1, SPP1, KLK13, FN1, CRISP3, EPHX3, COL5A2, ECM1, MMP12, MMP11, BGN, TMPRSS11E, SERPINB2, LAMC2, MFAP2, VCAN, COL1A1, IGFBP3, PLAU, IL36A", "2.95", "9.75E-05"], ["GOTERM_CC_DIRECT", "GO: 0005581~ collagen trimer", "7", "5.83", "2.94E-05", "COL3A1, COL6A3, COL1A1, SERPINH1, COL5A2, MMP1, TIMP1", "11.65", "3.52E-02"], ["GOTERM_MF_DIRECT", "GO: 0004867~ serine-type endopeptidase inhibitor activity", "7", "5.83", "4.74E-05", "COL6A3, SERPINE1, SERPINB2, SERPINB1, SERPINB13, SERPINH1, SPINK5", "10.69", "6.13E-02"], ["GOTERM_MF_DIRECT", "GO: 0004252~ serine-type endopeptidase activity", "10", "8.33", "5.41E-05", "FAP, MMP9, TMPRSS11E, KLK12, MMP3, MMP12, PLAU, MMP1, MMP11, KLK13", "5.81", "6.99E-02"], ["GOTERM_MF_DIRECT", "GO: 0002020~ protease binding", "7", "5.83", "5.95E-05", "FAP, SERPINE1, CST1, SERPINB13, ECM1, FN1, TIMP1", "10.26", "7.69E-02"], ["GOTERM_MF_DIRECT", "GO: 0005201~ extracellular matrix 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