Construction and comprehensive analysis of a novel prognostic signature associated with pyroptosis molecular subtypes in patients with pancreatic adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36817451", "kind": "science-record", "revision": 3, "content_hash": "sha256:8965cf9dbad0b2fba9505ada51a829fa239cb8df7df9d7625e72abeab8a8571d", "created_at": "2026-11-01T19:01:24Z", "updated_at": "2026-11-01T22:08:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction and comprehensive analysis of a novel prognostic signature associated with pyroptosis molecular subtypes in patients with pancreatic adenocarcinoma.", "doi": "10.3389/fimmu.2023.1111494", "pmid": "36817451", "authors": ["Qian Huang", "Xingyu Peng", "Qingqing Li", "Jinfeng Zhu", "Ju Xue", "Hua Jiang"], "journal": "Frontiers in immunology", "year": 2023, "abstract": "Background: Treatment of cancer with pyroptosis is an emerging strategy. Molecular subtypes based on pyroptosis-related genes(PRGs) seem to be considered more conducive to individualized therapy. It is meaningful to construct a pyroptosis molecular subtypes-related prognostic signature (PMSRPS) to predict the overall survival (OS) of patients with pancreatic adenocarcinoma(PAAD) and guide treatment.\nMethods: Based on the transcriptome data of 23 PRGs, consensus clustering was applied to divide the TCGA and GSE102238 combined cohort into three PRGclusters. Prognosis-related differentially expressed genes(DEGs) among PRGclusters were subjected to LASSO Cox regression analysis to determine a PMSRPS. External cohort and in vitro experiments were conducted to verify this PMSRPS. The CIBERSORT algorithm, the ESTIMATE algorithm and the Immunophenoscore (IPS) were used to analyze the infiltrating abundance of immune cells, the tumor microenvironment (TME), and the response to immunotherapy, respectively. Wilcoxon analysis was used to compare tumor mutational burden (TMB) and RNA stemness scores (RNAss) between groups. RT-qPCR and in vitro functional experiments were used for evaluating the expression and function of SFTA2.\nResults: Based on three PRGclusters, 828 DEGs were obtained and a PMSRPS was subsequently constructed. In internal and external validation, patients in the high-risk group had significantly lower OS than those in the low-risk group and PMSRPS was confirmed to be an independent prognostic risk factor for patients with PAAD with good predictive performance. Immune cell infiltration abundance and TME scores indicate patients in the high-risk group have typical immunosuppressive microenvironment characteristics. Analysis of IPS suggests patients in the high-risk group responded better to novel immune checkpoint inhibitors (ICIs) than PD1/CTLA4. The high-risk group had higher TMB and RNAss. In addition, 10 potential small-molecule compounds were screened out. Finally, we found that the mRNA expression of SFTA2 gene with the highest risk coefficient in PMSRPS was significantly higher in PAAD than in paracancerous tissues, and knockdown of it significantly delayed the progression of PAAD.\nConclusions: PMSRPS can well predict the prognosis, TME and immunotherapy response of patients with PAAD, identify potential drugs, and provide treatment guidance based on individual needs.", "claims": [{"id": "claim-method", "statement": "The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed on PRDEGs in the training cohort to construct a refined prognostic signature (28).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36817451", "locator": "sections[6] \"Establishment and identification of prognostic signature\" paragraph 2", "quote": "The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed on PRDEGs in the training cohort to construct a refined prognostic signature (28)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: The TCGA database can be found here: https://portal.gdc.cancer.gov/, the GEO database https://www.ncbi.nlm.nih.gov/geo/, the ICGC database https://dcc.icgc.org/, the GTEx database https://xenabrowser.net/datapages/, and the original data for experimental validation are available through corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36817451", "locator": "sections[29] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: The TCGA database can be found here: https://portal.gdc.cancer.gov/, the GEO database https://www.ncbi.nlm.nih.gov/geo/, the ICGC database https://dcc.icgc.org/, the GTEx database https://xenabrowser.net/datapages/, and the original data for experimental validation are available through corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The three-gene PMSRPS outperformed the Bai-Sig, Xiao-Sig, and Wu-Sig signatures when predicting 1-, 3-, and 5-year overall survival in patients with PAAD.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36817451", "locator": "sections[22] \"External cohort verification and performance comparison of PMSRPS\" paragraph 4", "quote": "The results showed that the AUCs of PMSRPS (0.676, 0.631, 0.600) for predicting the 1-, 3-, and 5-year overall survival of patients with PAAD were higher than those of Bai-Sig (0.609, 0.594, 0.542), Xiao-Sig (0.623, 0.614, 0.557) and Wu-Sig (0.667, 0.630, 0.551) ( Figures 7M–O )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The three-gene PMSRPS outperformed the Bai-Sig, Xiao-Sig, and Wu-Sig signatures when predicting 1-, 3-, and 5-year overall survival in patients with PAAD.", "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:36817451"], "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:GSE102238"], "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:GSE102238"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36817451", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2023.1111494", "sha256": "sha256:3220337f410c5eb69b56da28f31415fab62665b7f101ff87d7e57a9010533534", "bytes": 77655, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2023.1111494", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9935619", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE102238", "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=GSE102238", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE102238", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: The TCGA database can be found here: https://portal.gdc.cancer.gov/, the GEO database https://www.ncbi.nlm.nih.gov/geo/, the ICGC database https://dcc.icgc.org/, the GTEx database https://xenabrowser.net/datapages/, and the original data for experimental validation are available through corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: The TCGA database can be found here: https://portal.gdc.cancer.gov/, the GEO database https://www.ncbi.nlm.nih.gov/geo/, the ICGC database https://dcc.icgc.org/, the GTEx database https://xenabrowser.net/datapages/, and the original data for experimental validation are available through corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2731543", "GSM2731544", "GSM2731545", "GSM2731546", "GSM2731547", "GSM2731548", "GSM2731549", "GSM2731550", "GSM2731551", "GSM2731552", "GSM2731553", "GSM2731554", "GSM2731555", "GSM2731556", "GSM2731557", "GSM2731558", "GSM2731559", "GSM2731560", "GSM2731561", "GSM2731562", "GSM2731563", "GSM2731564", "GSM2731565", "GSM2731566", "GSM2731567", "GSM2731568", "GSM2731569", "GSM2731570", "GSM2731571", "GSM2731572", "GSM2731573", "GSM2731574", "GSM2731575", "GSM2731576", "GSM2731577", "GSM2731578", "GSM2731579", "GSM2731580", "GSM2731581", "GSM2731582", "GSM2731583", "GSM2731584", "GSM2731585", "GSM2731586", "GSM2731587", "GSM2731588", "GSM2731589", "GSM2731590", "GSM2731591", "GSM2731592", "GSM2731593", "GSM2731594", "GSM2731595", "GSM2731596", "GSM2731597", "GSM2731598", "GSM2731599", "GSM2731600", "GSM2731601", "GSM2731602", "GSM2731603", "GSM2731604", "GSM2731605", "GSM2731606", "GSM2731607", "GSM2731608", "GSM2731609", "GSM2731610", "GSM2731611", "GSM2731612", "GSM2731613", "GSM2731614", "GSM2731615", "GSM2731616", "GSM2731617", "GSM2731618", "GSM2731619", "GSM2731620", "GSM2731621", "GSM2731622", "GSM2731623", "GSM2731624", "GSM2731625", "GSM2731626", "GSM2731627", "GSM2731628", "GSM2731629", "GSM2731630", "GSM2731631", "GSM2731632", "GSM2731633", "GSM2731634", "GSM2731635", "GSM2731636", "GSM2731637", "GSM2731638", "GSM2731639", "GSM2731640", "GSM2731641", "GSM2731642"], "sample_count": 100, "group_sizes": null, "group_sizes_basis": null, "platform": "19072", "taxon": "Homo sapiens", "title": "Gene expression signatures associated with Perineural Invasion in pancreatic ductal adenocarcinoma", "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:GSE57495", "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=GSE57495", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE57495", "version": null, "note": "Publicly available datasets were analyzed in this study. 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RT-qPCR and in vitro functional experiments were use", "A stemness scores (RNAss) between groups. RT-qPCR and in vitro functional experiments were use", "ccording to standard guidelines. Samples and real-time quantitative PCR The tumor tissue and paired adjacent tissue", "respectively, and reverse transcription and real-time PCR were performed. The following primers used i"], "order_basis": "paper_text_order:1246", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["r in PAAD than in paracancerous tissues, and knockdown of it significantly delayed the progression", "Materials and methods Cell culture and transfection The human PAAD cell line CFPAC-1 was derived", "n Supplementary Table 3 . CFPAC-1 cells were transfected using Lipofectamine 3000 reagent (Invitrogen", "3), total RNA was extracted from tissues and transfected cells, respectively, and reverse transcripti"], "order_basis": "paper_text_order:2286", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["from Procell (CL-0059, Wuhan, China) and was cultured in a special medium (Procell, CM-0059) in a 37°"], "order_basis": "paper_text_order:2681", "id": "assay:3"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["al-mesenchymal transformation, resistance to apoptosis and antitumor drugs, and propensity to sprea"], "order_basis": "paper_text_order:6028", "id": "assay:4"}, {"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": ["The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed on PRDEGs in the training cohort to construct a refined prognostic signature (28)."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}