High Expression of Interferon Pathway Genes CXCL10 and STAT2 Is Associated with Activated T-Cell Signature and Better Outcome of Oral Cancer Patients.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35207629", "kind": "science-record", "revision": 4, "content_hash": "sha256:1b003f1329f9939e1670e4796b33f046ae49c9314e40a70248c4322d587f7c03", "created_at": "2026-11-01T17:36:58Z", "updated_at": "2026-11-01T22:48:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "High Expression of Interferon Pathway Genes CXCL10 and STAT2 Is Associated with Activated T-Cell Signature and Better Outcome of Oral Cancer Patients.", "doi": "10.3390/jpm12020140", "pmid": "35207629", "authors": ["Yun-Cian Huang", "Jau-Ling Huang", "Lu-Chia Tseng", "Ping-Hung Yu", "Si-Yun Chen", "Chang-Shen Lin"], "journal": "Journal of personalized medicine", "year": 2022, "abstract": "To improve the survival rate of cancer patients, biomarkers for both early diagnosis and patient stratification for appropriate therapeutics play crucial roles in precision oncology. Investigation of altered gene expression and the relevant molecular pathways in cancer cells are helpful for discovering such biomarkers. In this study, we explore the potential prognostic biomarkers for oral cancer patients through systematically analyzing five oral cancer transcriptomic data sets (TCGA, GSE23558, GSE30784, GSE37991, and GSE138206). Gene Set Enrichment Analysis (GSEA) was individually applied to each data set and the upregulated Hallmark molecular pathways of each data set were intersected to generate 13 common pathways including interferon-α/γ pathways. Among the 5 oral cancer data sets, 43 interferon pathway genes were commonly upregulated and 17 genes exhibited prognostic values in TCGA cohort. After validating in another oral cancer cohort (GSE65858), high expressions of C-X-C motif chemokine ligand 10 (CXCL10) and Signal transducer and activator of transcription 2 (STAT2) were confirmed to be good prognostic biomarkers. GSEA of oral cancers stratified by CXCL10/STAT2 expression showed that activation of T-cell pathways and increased tumor infiltration scores of Type 1 T helper (Th1) and CD8+ T cells were associated with high CXCL10/STAT2 expression. These results suggest that high CXCL10/STAT2 expression can predict a favorable outcome in oral cancer patients.", "claims": [{"id": "claim-method", "statement": "The patient overall survival (OS) in TCGA and GSE65858 oral cancer cohorts was analyzed by the web-based tools Kaplan-Meier plotter (http://kmplot.com/analysis/ accessed between 15 November 2020 and 4 April 2021) with “best cut-off” setting [19]. The IBM SPSS Statistics (version 22, Armonk, NY, USA) was used to compute hazard ratio (HR) of patient OS according to variables of CXCL10/STAT2 expression (HH versus LL), T-stage (T3–4 versus T1–2), N-stage (N1–3 versus N0), gender (male versus female), and age (>60-yr vs. <60-yr) by Cox model analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35207629", "locator": "sections[7] \"2.3. Kaplan-Meier Survival and Statistical Analyses\" paragraph 2", "quote": "The patient overall survival (OS) in TCGA and GSE65858 oral cancer cohorts was analyzed by the web-based tools Kaplan-Meier plotter (http://kmplot.com/analysis/ accessed between 15 November 2020 and 4 April 2021) with “best cut-off” setting [19]. The IBM SPSS Statistics (version 22, Armonk, NY, USA) was used to compute hazard ratio (HR) of patient OS according to variables of CXCL10/STAT2 expression (HH versus LL), T-stage (T3–4 versus T1–2), N-stage (N1–3 versus N0), gender (male versus female), and age (>60-yr vs. <60-yr) by Cox model analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data supporting reported results can be found through requesting the corresponding author. The TCGA and GEO oral cancer data sets can be accessed at https://portal.gdc.cancer.gov and https://www.ncbi.nlm.nih.gov/geo/ (data accessed on 15 July 2020), respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35207629", "locator": "sections[21] \"Data Availability Statement\" paragraph 2", "quote": "All data supporting reported results can be found through requesting the corresponding author. The TCGA and GEO oral cancer data sets can be accessed at https://portal.gdc.cancer.gov and https://www.ncbi.nlm.nih.gov/geo/ (data accessed on 15 July 2020), respectively."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using Kaplan-Meier and Cox analyses of the TCGA and GSE65858 oral cancer cohorts, coordinated high CXCL10/STAT2 expression predicted favorable overall survival, with univariate HH-versus-LL hazard ratios of 0.568 in TCGA and 0.225 in GSE65858.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35207629", "locator": "sections[12] \"3.3. High Expressions of CXCL10 and STAT2 Were Good Prognostic Factors\" paragraph 2", "quote": "The results of Kaplan-Meier survival analysis demonstrated that both the HH patient subgroups in TCGA (Figure 5C) and GSE65858 (Figure 5D) cohorts exhibited good prognosis. The hazard ratio (HR, HH versus LL) was 0.568 (p = 0.003) in TCGA and was 0.225 (p = 0.010) in GSE65858 in univariate Cox model analysis (Table 3)."}, {"asset": "source:pmid:35207629", "locator": "sections[5] \"2.1.2. Validation Data Sets\" paragraph 2", "quote": "The gene expression and clinical data of 83 oral cancers were extracted from GSE65858 (Germany) data set to validate the prognostic roles of interferon pathway genes discovered in TCGA oral cancer data set."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using Kaplan-Meier and Cox analyses of the TCGA and GSE65858 oral cancer cohorts, coordinated high CXCL10/STAT2 expression predicted favorable overall survival, with univariate HH-versus-LL hazard ratios of 0.568 in TCGA and 0.225 in GSE65858.", "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:35207629"], "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:GSE138206"], "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:GSE138206"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35207629", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/jpm12020140", "sha256": "sha256:92ecf36ebdd3c2f1d709e7ab1dba3603da489a11cb7976ed0e6f43c4c19d4a87", "bytes": 42745, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/jpm12020140", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8877377", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE138206", "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=GSE138206", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE138206", "version": null, "note": "All data supporting reported results can be found through requesting the corresponding author. 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"GSM1607950", "GSM1607951", "GSM1607952", "GSM1607953"], "sample_count": 270, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Gene expression patterns and TP53 mutations are associated with HPV RNA status, lymph node metastasis, and survival in head and neck cancer", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE138206 not downloaded", "asset:data:geo:GSE138206 licence not read", "asset:data:geo:GSE23558 not downloaded", "asset:data:geo:GSE23558 licence not read", "asset:data:geo:GSE30784 not downloaded", "asset:data:geo:GSE30784 licence not read", "asset:data:geo:GSE37991 not downloaded", "asset:data:geo:GSE37991 licence not read", "asset:data:geo:GSE65858 not downloaded", "asset:data:geo:GSE65858 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The patient overall survival (OS) in TCGA and GSE65858 oral cancer cohorts was analyzed by the web-based tools Kaplan-Meier plotter (http://kmplot.com/analysis/ accessed between 15 November 2020 and 4 April 2021) with “best cut-off” setting [19]. The IBM SPSS Statistics (version 22, Armonk, NY, USA) was used to compute hazard ratio (HR) of patient OS according to variables of CXCL10/STAT2 expression (HH versus LL), T-stage (T3–4 versus T1–2), N-stage (N1–3 versus N0), gender (male versus female), and age (>60-yr vs. <60-yr) by Cox model analysis."}}, {"id": "method-2", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Cox model"}}], "targets": [], "gaps": []}, "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": true, "required_operations": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "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": ["GSE23558", "GSE30784", "GSE37991", "GSE138206", "GSE65858"], "resolved_accessions": ["GSE23558", "GSE30784", "GSE37991", "GSE138206", "GSE65858"], "statements": ["All data supporting reported results can be found through requesting the corresponding author. The TCGA and GEO oral cancer data sets can be accessed at https://portal.gdc.cancer.gov and https://www.ncbi.nlm.nih.gov/geo/ (data accessed on 15 July 2020), respectively."], "basis": "The paper names GSE23558, GSE30784, GSE37991, GSE138206, GSE65858 in Gene Expression Omnibus and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:35207629", "data:geo:GSE138206"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE138206"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:35:47Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13701, "completion_tokens": 2955, "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:35207629", "type": "paper", "label": "pmid:35207629"}, {"id": "source:pmid:35207629", "type": "manuscript", "label": "PMID 35207629 full text"}, {"id": "data:geo:GSE138206", "type": "dataset", "label": "GEO GSE138206"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35207629", "type": "paper", "label": "pmid:35207629"}, {"id": "source:pmid:35207629", "type": "manuscript", "label": "PMID 35207629 full text"}, {"id": "data:geo:GSE138206", "type": "dataset", "label": "GEO GSE138206"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35207629", "type": "extraction", "used": ["source:pmid:35207629"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE138206", "type": "accession_resolution", "used": ["data:geo:GSE138206"], "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:35207629", "parent_hash": "sha256:e38368247d7af3637df3effa3b727fb32e101e91bd1adbe9c41e5e5c57d29825", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE138206 licence not read", "asset:data:geo:GSE138206 not downloaded", "asset:data:geo:GSE23558 licence not read", "asset:data:geo:GSE23558 not downloaded", "asset:data:geo:GSE30784 licence not read", "asset:data:geo:GSE30784 not downloaded", "asset:data:geo:GSE37991 licence not read", "asset:data:geo:GSE37991 not downloaded", "asset:data:geo:GSE65858 licence not read", "asset:data:geo:GSE65858 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The patient overall survival (OS) in TCGA and GSE65858 oral cancer cohorts was analyzed by the web-based tools Kaplan-Meier plotter (http://kmplot.com/analysis/ accessed between 15 November 2020 and 4 April 2021) with “best cut-off” setting [19]. The IBM SPSS Statistics (version 22, Armonk, NY, USA) was used to compute hazard ratio (HR) of patient OS according to variables of CXCL10/STAT2 expression (HH versus LL), T-stage (T3–4 versus T1–2), N-stage (N1–3 versus N0), gender (male versus female), and age (>60-yr vs. <60-yr) by Cox model analysis."], "order_basis": "analysis_only", "id": "assay:1"}]}