Comprehensive Profiling Reveals Prognostic and Immunogenic Characteristics of Necroptosis in Soft Tissue Sarcomas.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35663937", "kind": "science-record", "revision": 4, "content_hash": "sha256:b2df470d23b72a542671504a164f5efe34999f8b9d2bf8f6fa069c579ba545cf", "created_at": "2026-11-01T18:14:36Z", "updated_at": "2026-11-01T22:06:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive Profiling Reveals Prognostic and Immunogenic Characteristics of Necroptosis in Soft Tissue Sarcomas.", "doi": "10.3389/fimmu.2022.877815", "pmid": "35663937", "authors": ["Lin Qi", "Ruiling Xu", "Xiaolei Ren", "Wenchao Zhang", "Zhimin Yang", "Chao Tu", "Zhihong Li"], "journal": "Frontiers in immunology", "year": 2022, "abstract": "Soft tissue sarcomas (STSs) are heterogeneous malignancies derived from mesenchymal cells. Due to its rarity, heterogeneity, and limited overall response to chemotherapy, STSs represent a therapeutic challenge. Necroptosis is a novel therapeutic strategy for enhancing immunotherapy of cancer. Nevertheless, no research has explored the relationship between necroptosis-related genes (NRGs) and STSs. In this study, differentially expressed NRGs were identified using The Cancer Genome Atlas (TCGA) and The Cancer Genotype-Tissue Expression (GTEx) project. The expression levels of 34 NRGs were significantly different. Several key NRGs were validated using RT-qPCR and our own sequencing data. Patients with STSs were divided into two clusters using consensus cluster analysis, and significant differences were observed in their survival (p=0.002). We found the differentially expressed genes (DEGs) between the two clusters and carried out subsequent analysis. The necroptosis-related gene signatures with 10 key DEGs were identified with a risk score constructed. The prognosis of TCGA-SARC cohort with low necroptosis-related risk score was better (p<0.001). Meanwhile, the low-risk group had a significantly increased immune infiltration. Using the data of GSE17118 and another immunotherapy cohort as external validations, we observed significant survival differences between the two risk groups (p=0.019). The necroptosis-related risk score proved to be an independent prognostic factor, and a nomogram was further established and integrated with other clinical features. Notably, the necroptosis-related gene signature could also act as the prognostic indicator in other malignancies based on pan-cancer analysis. In summary, the study outlines NRGs in STSs and their potential role in prognosis and will be one of the important directions for future research.", "claims": [{"id": "claim-method", "statement": "DEGs with significant effect on survival rate were screened (p < 0.01), which were further entered into the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to narrow down the scope of gene selection using “glmnet” R package (Version 4.1-2).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35663937", "locator": "sections[8] \"Prognostic Model Development\" paragraph 2", "quote": "DEGs with significant effect on survival rate were screened (p < 0.01), which were further entered into the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to narrow down the scope of gene selection using “glmnet” R package (Version 4.1-2)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are publicly available. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE198568.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35663937", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are publicly available. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE198568."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Patients with STSs were divided into two clusters using consensus cluster analysis, and significant differences were observed in their survival (p=0.002).", "kind": "quantitative", "target": {"value": 0.002, "unit": "p-value", "tolerance": null, "source": "Patients with STSs were divided into two clusters using consensus cluster analysis, and significant differences were observed in their survival (p=0.002)."}, "evidence": [{"asset": "source:pmid:35663937", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Patients with STSs were divided into two clusters using consensus cluster analysis, and significant differences were observed in their survival (p=0.002)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Patients with STSs were divided into two clusters using consensus cluster analysis, and significant differences were observed in their survival (p=0.002).", "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:35663937"], "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:GSE17118"], "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:GSE17118"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35663937", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2022.877815", "sha256": "sha256:4738837cf827c2b780b6fc1dabe4bff396bcbe8dfef271842bea3f36dda66471", "bytes": 61201, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2022.877815", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9159500", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE17118", "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=GSE17118", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE17118", "version": null, "note": "The original contributions presented in the study are publicly available. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE198568.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are publicly available. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE198568.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM428160", "GSM428161", "GSM428162", "GSM428163", "GSM428164", "GSM428165", "GSM428166", "GSM428167", "GSM428168", "GSM428169", "GSM428170", "GSM428171", "GSM428172", "GSM428173", "GSM428174", "GSM428175", "GSM428176", "GSM428177", "GSM428178", "GSM428179", "GSM428180", "GSM428181", "GSM428182", "GSM428183", "GSM428184", "GSM428185", "GSM428186", "GSM428187", "GSM428188", "GSM428189", "GSM428190", "GSM428191", "GSM428192", "GSM428193", "GSM428194", "GSM428195", "GSM428196", "GSM428197", "GSM428198", "GSM428199", "GSM428200", "GSM428201", "GSM428202", "GSM428203", "GSM428204", "GSM428205", "GSM428206", "GSM428207", "GSM428208", "GSM428209", "GSM428210", "GSM428211", "GSM428212", "GSM428213", "GSM428214", "GSM428215", "GSM428216", "GSM428217", "GSM428218", "GSM428219"], "sample_count": 60, "group_sizes": null, "group_sizes_basis": null, "platform": "6480", "taxon": "Homo sapiens", "title": "TCEAL7 Inhibition of c-Myc Activity in Alternative Lengthening of Telomeres Regulates hTERT Expression", "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:GSE198568", "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=GSE198568", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE198568", "version": null, "note": "The original contributions presented in the study are publicly available. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE198568.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are publicly available. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE198568.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM5952362", "GSM5952363", "GSM5952364", "GSM5952365", "GSM5952366", "GSM5952367", "GSM5952368", "GSM5952369"], "sample_count": 8, "group_sizes": null, "group_sizes_basis": null, "platform": "26167", "taxon": "Homo sapiens", "title": "Full-length transcriptome sequencing reveals gene expression signatures in human soft tissue sarcomas", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE17118 not downloaded", "asset:data:geo:GSE17118 licence not read", "asset:data:geo:GSE198568 not downloaded", "asset:data:geo:GSE198568 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "DEGs with significant effect on survival rate were screened (p < 0.01), which were further entered into the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to narrow down the scope of gene selection using “glmnet” R package (Version 4.1-2)."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {"p_value": "the two groups, and the p value of each gene was calcul"}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "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": 0.8, "band": "high", "quote": "KM"}}, {"id": "method-4", "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": 0.8, "band": "high", "quote": "log-rank"}}, {"id": "method-5", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "Principal component analysis"}}, {"id": "method-6", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "GO enrichment"}}, {"id": "method-7", "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": "χ2"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "chi_square_test", "expected_value": 0.002, "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": ["method.reader_differs_from_extractor"]}, "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["GSE17118", "GSE198568"], "resolved_accessions": ["GSE17118", "GSE198568"], "statements": ["The original contributions presented in the study are publicly available. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE198568."], "basis": "The paper names GSE17118, GSE198568 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": ["cox_ph"], "assets": ["source:pmid:35663937", "data:geo:GSE17118"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE17118"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:48:58Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 18124, "completion_tokens": 1506, "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:35663937", "type": "paper", "label": "pmid:35663937"}, {"id": "source:pmid:35663937", "type": "manuscript", "label": "PMID 35663937 full text"}, {"id": "data:geo:GSE17118", "type": "dataset", "label": "GEO GSE17118"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35663937", "type": "paper", "label": "pmid:35663937"}, {"id": "source:pmid:35663937", "type": "manuscript", "label": "PMID 35663937 full text"}, {"id": "data:geo:GSE17118", "type": "dataset", "label": "GEO GSE17118"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35663937", "type": "extraction", "used": ["source:pmid:35663937"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE17118", "type": "accession_resolution", "used": ["data:geo:GSE17118"], "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:35663937", "parent_hash": "sha256:72f794de8fbea3a2d9aad653baf3b1bdb198e2c213aa1750d93ba5de4b089921", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE17118 licence not read", "asset:data:geo:GSE17118 not downloaded", "asset:data:geo:GSE198568 licence not read", "asset:data:geo:GSE198568 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["erent. Several key NRGs were validated using RT-qPCR and our own sequencing data. Patients with S", "nt. Several key NRGs were validated using RT-qPCR and our own sequencing data. Patients with S"], "order_basis": "paper_text_order:728", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["n of NRGs. SW-982, SW-872, and hSS-005R were cultured in Dulbecco’s modified Eagle medium (DMEM) (Gib", "rum (FBS) (Gibco, United States). Cells were cultured in a humidified incubator (Thermo Fisher Scient"], "order_basis": "paper_text_order:2468", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["DEGs with significant effect on survival rate were screened (p < 0.01), which were further entered into the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to narrow down the scope of gene selection using “glmnet” R package (Version 4.1-2)."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}