SPP1 and CXCL9 Promote Non-alcoholic Steatohepatitis Progression Based on Bioinformatics Analysis and Experimental Studies.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35514751", "kind": "science-record", "revision": 4, "content_hash": "sha256:1b172501e513096bf23fb72efa7cb909273434f92b57d7ed109bdee9dd21c50c", "created_at": "2026-11-01T18:14:24Z", "updated_at": "2026-11-01T22:06:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "SPP1 and CXCL9 Promote Non-alcoholic Steatohepatitis Progression Based on Bioinformatics Analysis and Experimental Studies.", "doi": "10.3389/fmed.2022.862278", "pmid": "35514751", "authors": ["Wen Wang", "Xiaojing Liu", "Peiyao Wei", "Feng Ye", "Yunru Chen", "Lei Shi", "Xi Zhang", "Jianzhou Li", "Shumei Lin", "Xueliang Yang"], "journal": "Frontiers in medicine", "year": 2022, "abstract": "Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is a major chronic liver disease worldwide, and non-alcoholic steatohepatitis (NASH) is one of its pathological subtypes. The pathogenesis of NASH has not yet been fully elucidated. The purpose of this study was to identify the hub genes and pathways involved in NASH using bioinformatics methods. The hub genes were confirmed in human and animal models.\nMaterials and Methods: Three Gene Expression Omnibus (GEO) datasets (GSE48452, GSE58979, and GSE151158) of NASH patients and healthy controls were included in the study. We used GEO2R to identify differentially expressed genes (DEGs) between NASH patients and healthy controls. Functional enrichment analyses were then performed to explore the potential functions and pathways of the DEGs. In all DEGs, only two genes were highly expressed in NASH patients throughout the three datasets; these two genes, SPP1 and CXCL9, were further studied. Serum and liver tissues from NASH patients and healthy controls were collected. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured in NASH patients and healthy controls. Liver tissues were stained with hematoxylin and eosin. Immunohistochemical staining was used to evaluate the expression levels of the two genes in liver tissues. Male C57BL/6J mice were fed a methionine choline-deficient (MCD) diet for 8 weeks, after which serum ALT and AST levels were measured and liver tissues were stained.\nResults: SPP1 and CXCL9 were the hub genes detected in the three datasets. \"Lipid metabolism,\" \"inflammatory response,\" and \"lymphocyte activation\" were the most significant biological functions in GSE48452, GSE58979, and GSE151158, respectively. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the toll-like receptor signaling pathway was significantly enriched in NASH patients. Serum ALT and AST levels were significantly increased in NASH patients compared to healthy controls. Liver tissues had more serious steatosis, hepatocyte ballooning degeneration, and lobular inflammatory infiltration, and the expression of SPP1 and CXCL9 in liver cells was significantly upregulated in NASH patients compared to healthy controls. MCD diet mice were consistent with NASH patients.\nConclusion: SPP1 and CXCL9 may play important roles in NASH pathogenesis and could be potential therapeutic targets and biomarkers of NASH in the future. Further experimental studies are needed to confirm our results.", "claims": [{"id": "claim-method", "statement": "The original microarray data were analyzed using the online tool GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r), which allows researchers to identify DEGs in each group. Statistical analysis between groups used an unpaired two-tailed Student's t-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35514751", "locator": "sections[4] \"Identification of DEGs\" paragraph 2", "quote": "The original microarray data were analyzed using the online tool GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r), which allows researchers to identify DEGs in each group."}, {"asset": "source:pmid:35514751", "locator": "sections[10] \"Statistical Analysis\" paragraph 2", "quote": "Statistical analysis between groups used an unpaired two-tailed Student's t-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.ncbi.nlm.nih.gov/geo/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35514751", "locator": "sections[17] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.ncbi.nlm.nih.gov/geo/."}], "state": "complete"}, {"id": "claim-target-result", "statement": "SPP1 and CXCL9 were identified as the hub genes in all three NASH datasets.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35514751", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "SPP1 and CXCL9 were the hub genes detected in the three datasets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "SPP1 and CXCL9 were identified as the hub genes in all three NASH datasets.", "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:35514751"], "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:GSE151158"], "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:GSE151158"], "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:35514751", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmed.2022.862278", "sha256": "sha256:d0561287667b19cee10b351ee4769bf049873f354301169a98799c0fd73c7e52", "bytes": 25035, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmed.2022.862278", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9063562", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE151158", "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=GSE151158", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE151158", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.ncbi.nlm.nih.gov/geo/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.ncbi.nlm.nih.gov/geo/.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4567420", "GSM4567421", "GSM4567422", "GSM4567423", "GSM4567424", "GSM4567425", "GSM4567426", "GSM4567427", "GSM4567428", "GSM4567429", "GSM4567430", "GSM4567431", "GSM4567432", "GSM4567433", "GSM4567434", "GSM4567435", "GSM4567436", "GSM4567437", "GSM4567438", "GSM4567439", "GSM4567440", "GSM4567441", "GSM4567442", "GSM4567443", "GSM4567444", "GSM4567445", "GSM4567446", "GSM4567447", "GSM4567448", "GSM4567449", "GSM4567450", "GSM4567451", "GSM4567452", "GSM4567453", "GSM4567454", "GSM4567455", "GSM4567456", "GSM4567457", "GSM4567458", "GSM4567459", "GSM4567460", "GSM4567461", "GSM4567462", "GSM4567463", "GSM4567464", "GSM4567465", "GSM4567466", "GSM4567467", "GSM4567468", "GSM4567469", "GSM4567470", "GSM4567471", "GSM4567472", "GSM4567473", "GSM4567474", "GSM4567475", "GSM4567476", "GSM4567477", "GSM4567478", "GSM4567479", "GSM4567480", "GSM4567481", "GSM4567482", "GSM4567483", "GSM4567484", "GSM4567485"], "sample_count": 66, "group_sizes": null, "group_sizes_basis": null, "platform": "28577", "taxon": "Homo sapiens; blank sample", "title": "Transcriptional analysis of non-fibrotic NAFLD progression", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE48452", "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=GSE48452", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE48452", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.ncbi.nlm.nih.gov/geo/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.ncbi.nlm.nih.gov/geo/.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1178970", "GSM1178971", "GSM1178972", "GSM1178973", "GSM1178974", "GSM1178975", "GSM1178976", "GSM1178977", "GSM1178978", "GSM1178979", "GSM1178980", "GSM1178981", "GSM1178982", "GSM1178983", "GSM1178984", "GSM1178985", "GSM1178986", "GSM1178987", "GSM1178988", "GSM1178989", "GSM1178990", "GSM1178991", "GSM1178992", "GSM1178993", "GSM1178994", "GSM1178995", "GSM1178996", "GSM1178997", "GSM1178998", "GSM1178999", "GSM1179000", "GSM1179001", "GSM1179002", "GSM1179003", "GSM1179004", "GSM1179005", "GSM1179006", "GSM1179007", "GSM1179008", "GSM1179009", "GSM1179010", "GSM1179011", "GSM1179012", "GSM1179013", "GSM1179014", "GSM1179015", "GSM1179016", "GSM1179017", "GSM1179018", "GSM1179019", "GSM1179020", "GSM1179021", "GSM1179022", "GSM1179023", "GSM1179024", "GSM1179025", "GSM1179026", "GSM1179027", "GSM1179028", "GSM1179029", "GSM1179030", "GSM1179031", "GSM1179032", "GSM1179033", "GSM1179034", "GSM1179035", "GSM1179036", "GSM1179037", "GSM1179038", "GSM1179039", "GSM1179040", "GSM1179041", "GSM1179042"], "sample_count": 73, "group_sizes": null, "group_sizes_basis": null, "platform": "11532", "taxon": "Homo sapiens", "title": "Human liver biopsy of different phases from control to NASH", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE58979", "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=GSE58979", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE58979", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.ncbi.nlm.nih.gov/geo/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.ncbi.nlm.nih.gov/geo/.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1423267", "GSM1423268", "GSM1423269", "GSM1423270", "GSM1423271", "GSM1423272", "GSM1423273", "GSM1423274", "GSM1423275", "GSM1423276", "GSM1423277", "GSM1423278", "GSM1423279", "GSM1423280", "GSM1423281", "GSM1423282", "GSM1423283", "GSM1423284", "GSM1423285", "GSM1423286", "GSM1423287", "GSM1423288", "GSM1423289", "GSM1423290", "GSM1423291", "GSM1423292", "GSM1423293", "GSM1423294", "GSM1423295", "GSM1423296", "GSM1423297", "GSM1423298", "GSM1423299", "GSM1423300", "GSM1423301", "GSM1423302", "GSM1423303", "GSM1423304", "GSM1423305", "GSM1423306", "GSM1423307", "GSM1423308", "GSM1423309", "GSM1423310", "GSM1423311", "GSM1423312", "GSM1423313", "GSM1423314", "GSM1423315", "GSM1423316", "GSM1423317", "GSM1423318", "GSM1423319"], "sample_count": 53, "group_sizes": null, "group_sizes_basis": null, "platform": "15207", "taxon": "Homo sapiens", "title": "Gene expression in subcutaneous and visceral fat predicts liver histology in morbidly obese patients", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE151158 not downloaded", "asset:data:geo:GSE151158 licence not read", "asset:data:geo:GSE48452 not downloaded", "asset:data:geo:GSE48452 licence not read", "asset:data:geo:GSE58979 not downloaded", "asset:data:geo:GSE58979 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": "reordered", "quote": "The original microarray data were analyzed using the online tool GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r), which allows researchers to identify DEGs in each group. Statistical analysis between groups used an unpaired two-tailed Student's t-test."}}], "targets": [], "gaps": ["method.student_t"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE48452", "GSE58979", "GSE151158"], "resolved_accessions": ["GSE48452", "GSE58979", "GSE151158"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.ncbi.nlm.nih.gov/geo/."], "basis": "The paper names GSE48452, GSE58979, GSE151158 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:35514751", "data:geo:GSE151158"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE151158"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:44:51Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 7781, "completion_tokens": 1895, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:35514751", "type": "paper", "label": "pmid:35514751"}, {"id": "source:pmid:35514751", "type": "manuscript", "label": "PMID 35514751 full text"}, {"id": "data:geo:GSE151158", "type": "dataset", "label": "GEO GSE151158"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35514751", "type": "paper", "label": "pmid:35514751"}, {"id": "source:pmid:35514751", "type": "manuscript", "label": "PMID 35514751 full text"}, {"id": "data:geo:GSE151158", "type": "dataset", "label": "GEO GSE151158"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35514751", "type": "extraction", "used": ["source:pmid:35514751"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE151158", "type": "accession_resolution", "used": ["data:geo:GSE151158"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:35514751", "parent_hash": "sha256:5ff9d9a8d73119d601b4c9f16af93a52acc0f8e0d52a97a4b928cf63b9597d87", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE151158 licence not read", "asset:data:geo:GSE151158 not downloaded", "asset:data:geo:GSE48452 licence not read", "asset:data:geo:GSE48452 not downloaded", "asset:data:geo:GSE58979 licence not read", "asset:data:geo:GSE58979 not downloaded", "execution.not_run", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "assays": [{"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ues were stained with hematoxylin and eosin. Immunohistochemical staining was used to evaluate the expression", "nts compared to the HC group (Figures 3B,C). Immunohistochemical results showed that the expression levels of", "l indices change, morphological analysis and immunohistochemistry images of the expression of SPP1 and CXCL9 i", "SH and HC group of human liver samples using immunohistochemical staining (40×). The red arrows represent SPP"], "order_basis": "paper_text_order:1309", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["he two genes in liver tissues. Male C57BL/6J mice were fed a methionine choline-deficient (MCD) die", "ients compared to healthy controls. MCD diet mice were consistent with NASH patients. Conclusion: S", "Animal Center of Xi'an Jiaotong University. Mice were housed in an animal center with a light-dark"], "order_basis": "paper_text_order:1430", "id": "assay:2"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The original microarray data were analyzed using the online tool GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r), which allows researchers to identify DEGs in each group. Statistical analysis between groups used an unpaired two-tailed Student's t-test."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}