← All .science files
pmid:36147910
Mesenchymal gene expression subtyping analysis for early-stage human papillomavirus-negative head and neck squamous cell carcinoma reveals prognostic and predictive applications.
Gregory M Mayhew · Joshua M Uronis · David Neil Hayes · Jose P Zevallos
Frontiers in oncology · 2022 doi:10.3389/fonc.2022.954037
Paper
complete
Experiment
complete
Data
partial
Analysis
complete
Execution
absent
Execution evidence has not yet been added to this .science file. Explore its methods, data and open questions to plan the next step.
Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
paper object · 10 fields
authors array · 4 items
claims array · 3 items
[0] object · 6 fields
evidence array · 1 item
[0] object · 3 fields
[1] object · 6 fields
[2] object · 6 fields
target object · 4 fields
evidence array · 1 item
[0] object · 3 fields
gaps array · 0 items
experiment object · 8 fields
steps array · 3 items
[0] object · 13 fields
parameters object · 0 fields
inputs array · 1 item
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
[1] object · 13 fields
parameters object · 0 fields
inputs array · 1 item
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
[2] object · 13 fields
parameters object · 0 fields
inputs array · 1 item
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
materials array · 0 items
instruments array · 0 items
reagents array · 0 items
conditions object · 0 fields
gaps array · 0 items
data object · 3 fields
assets array · 2 items
[0] object · 15 fields
structure object · 4 fields
[1] object · 15 fields
structure object · 15 fields
sample_accessions array · 43 items
gaps array · 2 items
analysis object · 4 fields
methods array · 3 items
[0] object · 10 fields
dsl_operations array · 1 item
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[1] object · 10 fields
dsl_operations array · 1 item
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[2] object · 10 fields
dsl_operations array · 1 item
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
targets array · 1 item
[0] object · 8 fields
gaps array · 0 items
capability object · 3 fields
requirements array · 1 item
[0] object · 6 fields
assay_families array · 9 items
gaps array · 0 items
readiness object · 8 fields
axes object · 3 fields
method object · 5 fields
required_operations array · 1 item
missing_operations array · 0 items
capability object · 4 fields
data object · 6 fields
accessions array · 1 item
resolved_accessions array · 1 item
statements array · 1 item
can_run object · 3 fields
dsl_operations array · 1 item
assets array · 2 items
steps array · 1 item
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
gaps array · 0 items
review object · 5 fields
machine_critique object · 5 fields
reader object · 5 fields
evidence_check object · 2 fields
usage object · 3 fields
stages array · 1 item
[0] object · 4 fields
gaps array · 3 items
provenance object · 7 fields
entities array · 3 items
activities array · 3 items
[0] object · 4 fields
used array · 3 items
[0] object · 3 fields
[1] object · 3 fields
[2] object · 3 fields
[1] object · 4 fields
agents array · 2 items
lineage object · 4 fields
gaps array · 6 items
assays array · 2 items
[0] object · 11 fields
required_operations array · 0 items
source_hashes object · 1 field
evidence array · 2 items
[1] object · 11 fields
required_operations array · 1 item
source_hashes object · 1 field
evidence array · 1 item
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36147910", "kind": "science-record", "revision": 3, "content_hash": "sha256:2d58ce315696b7358b204c8b4e77088b856c2bd1a97330ab9c30f7aa68bc1d64", "created_at": "2026-11-01T18:15:26Z", "updated_at": "2026-11-01T21:29:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Mesenchymal gene expression subtyping analysis for early-stage human papillomavirus-negative head and neck squamous cell carcinoma reveals prognostic and predictive applications.", "doi": "10.3389/fonc.2022.954037", "pmid": "36147910", "authors": ["Gregory M Mayhew", "Joshua M Uronis", "David Neil Hayes", "Jose P Zevallos"], "journal": "Frontiers in oncology", "year": 2022, "abstract": "Patients with oral cavity squamous cell carcinoma (OCSCC) are predominantly human papillomavirus (HPV)(-), and treatment typically involves surgical resection ± neck dissection, followed by radiation ± chemotherapy. We previously described four mRNA expression patterns (classical, atypical, basal, and mesenchymal), each with unique genomic features and prognosis. Here, we examine the clinical utility of gene expression subtyping in head and neck squamous cell carcinoma (HNSCC) and introduce potentially predictive applications in HPV(-) OCSCC. A retrospective genomic database analysis was performed including 562 HNSCC patients from MD Anderson (MDA-GSE41116) and The Cancer Genome Atlas (TCGA). Samples were assigned molecular subtypes (classical, atypical, basal, and mesenchymal) using an 88-gene classifier. HPV status was determined by gene expression. The clinical endpoint was overall survival censured at 36 months. The Kaplan-Meier plots and log-rank tests were used to investigate associations between clinical variables and survival. Of the 418 TCGA training patients who met analysis criteria, nearly 20% presented as stage I/II. Among node(-) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease. This was confirmed in the MDA validation cohort. Node(-) non-mesenchymal OCSCC patients had far better survival compared to node(-) mesenchymal, and all node(+) patients had similarly poor survival. These findings suggest that the mesenchymal subtype is associated with poor survival in surgically resected, early-stage, node(-) OCSCC otherwise expected to have favorable outcomes. These findings highlight the potential value of gene expression subtyping as a pathology adjunct for prognostication and treatment decision-making in OCSCC patients.", "claims": [{"id": "claim-method", "statement": "The Kaplan–Meier plots and the log-rank test were used to assess univariate associations between survival and study parameters. Cox models were used to check associations with adjustment for potential confounders.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36147910", "locator": "sections[5] \"Clinical data and statistical analysis\" paragraph 2", "quote": "The Kaplan–Meier plots and the log-rank test were used to assess univariate associations between survival and study parameters. Cox models were used to check associations with adjustment for potential confounders."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36147910", "locator": "sections[10] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Among node(−) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease.", "kind": "quantitative", "target": {"value": 0.021, "unit": "p-value", "tolerance": null, "source": "Among node(−) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease."}, "evidence": [{"asset": "source:pmid:36147910", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Among node(−) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Among node(−) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease.", "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:36147910"], "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:GSE41116"], "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:GSE41116"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36147910", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2022.954037", "sha256": "sha256:57ddd70605340384ace15397fd1491a7849128df72364744352976676b03c167", "bytes": 36161, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2022.954037", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9486405", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE41116", "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=GSE41116", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE41116", "version": null, "note": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1008824", "GSM1008825", "GSM1008826", "GSM1008827", "GSM1008828", "GSM1008829", "GSM1008830", "GSM1008831", "GSM1008832", "GSM1008833", "GSM1008834", "GSM1008835", "GSM1008836", "GSM1008837", "GSM1008838", "GSM1008839", "GSM1008840", "GSM1008841", "GSM1008842", "GSM1008843", "GSM1008844", "GSM1008845", "GSM1008846", "GSM1008847", "GSM1008848", "GSM1008849", "GSM1008850", "GSM1008851", "GSM1008852", "GSM1008853", "GSM1008854", "GSM1008855", "GSM1008856", "GSM1008857", "GSM1008858", "GSM1008859", "GSM1008860", "GSM1008861", "GSM1008862", "GSM1008863", "GSM1008864", "GSM1008865", "GSM1008866"], "sample_count": 43, "group_sizes": null, "group_sizes_basis": null, "platform": "5175", "taxon": "Homo sapiens", "title": "Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers (mRNA)", "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:GSE41116 not downloaded", "asset:data:geo:GSE41116 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The Kaplan–Meier plots and the log-rank test were used to assess univariate associations between survival and study parameters. Cox models were used to check associations with adjustment for potential confounders."}}, {"id": "method-2", "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": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"id": "method-3", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "chi-square"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "chi_square_test", "expected_value": 0.021, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "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": ["logrank_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: log_rank_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": ["GSE41116"], "resolved_accessions": ["GSE41116"], "statements": ["The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE41116 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": ["logrank_test"], "assets": ["source:pmid:36147910", "data:geo:GSE41116"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE41116"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:06:49Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9860, "completion_tokens": 2474, "cached_tokens": 256}}, "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:36147910", "type": "paper", "label": "pmid:36147910"}, {"id": "source:pmid:36147910", "type": "manuscript", "label": "PMID 36147910 full text"}, {"id": "data:geo:GSE41116", "type": "dataset", "label": "GEO GSE41116"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36147910", "type": "paper", "label": "pmid:36147910"}, {"id": "source:pmid:36147910", "type": "manuscript", "label": "PMID 36147910 full text"}, {"id": "data:geo:GSE41116", "type": "dataset", "label": "GEO GSE41116"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36147910", "type": "extraction", "used": ["source:pmid:36147910"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE41116", "type": "accession_resolution", "used": ["data:geo:GSE41116"], "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:36147910", "parent_hash": "sha256:51328367eddce7b6d53de782461e8a25086aed82eb3527e257acb82497669c5e", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE41116 licence not read", "asset:data:geo:GSE41116 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["cal datasets. HPV positivity was assessed by RNA-seq evaluation of HPV-aligned sequences in HPV t", "e.niaid.nih.gov/. Read counts >1,000 for HPV RNA-seq (TCGA) or HPV E6 gene expression (18) were u"], "order_basis": "paper_text_order:3486", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["logrank_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The Kaplan–Meier plots and the log-rank test were used to assess univariate associations between survival and study parameters. Cox models were used to check associations with adjustment for potential confounders."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}