Comprehensive Analysis of the Immune Infiltrates of Pyroptosis in Kidney Renal Clear Cell Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34568046", "kind": "science-record", "revision": 8, "content_hash": "sha256:58b2a8a93401f41343d12490ba8de1b9387deedf02bb20f317340487313a367c", "created_at": "2026-11-01T15:41:54Z", "updated_at": "2026-11-01T22:47:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive Analysis of the Immune Infiltrates of Pyroptosis in Kidney Renal Clear Cell Carcinoma.", "doi": "10.3389/fonc.2021.716854", "pmid": "34568046", "authors": ["Zhuolun Sun", "Changying Jing", "Xudong Guo", "Mingxiao Zhang", "Feng Kong", "Zhenqing Wang", "Shaobo Jiang", "Hanbo Wang"], "journal": "Frontiers in oncology", "year": 2021, "abstract": "Kidney renal clear cell carcinoma (KIRC) has long been identified as a highly immune-infiltrated tumor. However, the underlying role of pyroptosis in the tumor microenvironment (TME) of KIRC remains poorly described. Herein, we systematically analyzed the prognostic value, role in the TME, response to ICIs, and drug sensitivity of pyroptosis-related genes (PRGs) in KIRC patients based on The Cancer Genome Atlas (TCGA) database. Cluster 2, by consensus clustering for 24 PRGs, presented a poor prognosis, likely because malignancy-related hallmarks were remarkably enriched. Additionally, we constructed a prognostic prediction model that discriminated well between high- and low-risk patients and was further confirmed in external E-MTAB-1980 cohort and HSP cohort. By further analyzing the TME based on the risk model, higher immune cell infiltration and lower tumor purity were found in the high-risk group, which presented a poor prognosis. Patients with high risk scores also exhibited higher ICI expression, indicating that these patients may be more prone to profit from ICIs. The sensitivity to anticancer drugs that correlated with model-related genes was also identified. Collectively, the pyroptosis-related prognosis risk model may improve prognostic information and provide directions for current research investigations on immunotherapeutic strategies for KIRC patients.", "claims": [{"id": "claim-method", "statement": "Kaplan-Meier analysis was used to evaluate OS, and the log-rank test was used to compare the OS between groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34568046", "locator": "sections[12] \"Statistical Analysis\" paragraph 2", "quote": "Kaplan-Meier analysis was used to evaluate OS, and the log-rank test was used to compare the OS between groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA (https://tcga-data.nci.nih.gov/tcga/), ArrayExpress (https://www.ebi.ac.uk/arrayexpress/), TIMER (https://cistrome.shinyapps.io/timer/), and GDSC (https://www.cancerrxgene.org/) websites.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34568046", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA (https://tcga-data.nci.nih.gov/tcga/), ArrayExpress (https://www.ebi.ac.uk/arrayexpress/), TIMER (https://cistrome.shinyapps.io/timer/), and GDSC (https://www.cancerrxgene.org/) websites."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:34568046"], "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:E-MTAB-1980"], "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:E-MTAB-1980"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34568046", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2021.716854", "sha256": "sha256:c5e0b3998db7dbef75d697dc12fedfe66a14f68076442f845c8b3d565eaceee1", "bytes": 50878, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2021.716854", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8459616", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:E-MTAB-1980", "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=E-MTAB-1980", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "E-MTAB-1980", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA (https://tcga-data.nci.nih.gov/tcga/), ArrayExpress (https://www.ebi.ac.uk/arrayexpress/), TIMER (https://cistrome.shinyapps.io/timer/), and GDSC (https://www.cancerrxgene.org/) websites.", "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: TCGA (https://tcga-data.nci.nih.gov/tcga/), ArrayExpress (https://www.ebi.ac.uk/arrayexpress/), TIMER (https://cistrome.shinyapps.io/timer/), and GDSC (https://www.cancerrxgene.org/) websites.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": null, "resolution_checked_at": "2026-10-31T18:28:57Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:34568046:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2fc96313d20d8b1862aa4e775f5d36d62b4a10d4dd738aabe021548083bfb3d8", "bytes": 1534, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#d31e284", "version": null, "note": "Characteristics of all patients included in this study.", "structure": {"pmcid": "PMC8459616", "section_index": 3, "section_title": "Data Source", "row_count": 33, "column_count": 4}, "table": {"label": "Table 1", "caption": "Characteristics of all patients included in this study.", "rows": [["Variable", "Training cohort (n = 317)", "Testing cohort (n = 208)", "Entire cohort (n = 525)"], ["Number (%)", "Number (%)", "Number (%)"], ["Age", "", "", ""], ["≤60", "158(49.84)", "106(50.96)", "264(50.29)"], [">60", "159(50.16)", "102(49.04)", "261(49.71)"], ["Gender", "", "", ""], ["Female", "109(34.38)", "73(35.1)", "182(34.67)"], ["Male", "208(65.62)", "135(64.9)", "343(65.33)"], ["Grade", "", "", ""], ["G1", "8(2.52)", "5(2.40)", "13(2.48)"], ["G2", "131(41.32)", "95(46.67)", "226(43.05)"], ["G3", "127(40.06)", "77(37.02)", "204(38.86)"], ["G4", "47(14.83)", "27(12.98)", "74(14.10)"], ["unknow", "4(1.26)", "4(1.92)", "8(1.52)"], ["AJCC stage", "", "", ""], ["I", "147(46.37)", "114(71.28)", "26149.71)"], ["II", "42(13.25)", "14(6.73)", "56(10.67)"], ["III", "75(23.66)", "48(23.08)", "123(23.43)"], ["IV", "52(16.40)", "30(14.42)", "82(15.62)"], ["unknow", "1(0.32)", "2(0.96)", "3(0.57)"], ["T stage", "", "", ""], ["T1", "150(47.32)", "117(56.25)", "267(50.86)"], ["T2", "49(15.46)", "19(9.13)", "68(12.95)"], ["T3", "111(35.02)", "68(23.69)", "179(34.1)"], ["T4", "7(2.21)", "4(1.92)", "11(2.10)"], ["N stage", "", "", ""], ["N0", "138(43.53)", "99(47.6)", "237(45.14)"], ["N1-3", "11(3.47)", "5(2.4)", "16(3.05)"], ["unknow", "168(53)", "104(50)", "272(51.81)"], ["M stage", "", "", ""], ["M0", "252(79.5)", "165(79.33)", "417(79.43)"], ["M1", "49(15.46)", "29(13.94)", "78(14.86)"], ["unknow", "16(5.05)", "14(3.76)", "30(5.71)"]], "row_count": 33, "column_count": 4, "numeric_cells": 78, "header_rows": 2, "locator": "section[3]/table-wrap[1]#d31e284"}}, {"id": "asset:table:pmid:34568046:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6b427bd847b7a3540150e17606d366d378d4c1b1d68e060b33164a9f51cad8e2", "bytes": 1117, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[2]#d31e581", "version": null, "note": null, "structure": {"pmcid": "PMC8459616", "section_index": 3, "section_title": "Data Source", "row_count": 33, "column_count": 3}, "table": {"label": null, "caption": null, "rows": [["Variable", "E-MTAB-1980 cohort (n = 101)", "HSP cohort (n = 186)"], ["Number (%)", "Number (%)"], ["Age", "", ""], ["≤60", "44(41.90)", "132(70.96)"], [">60", "57(58.10)", "54(29.04)"], ["Gender", "", ""], ["Female", "24(23.76)", "121(65.05)"], ["Male", "77(76.24)", "55(34.95)"], ["Grade", "", ""], ["G1", "13(12.87)", "44(23.66)"], ["G2", "59(58.41)", "102(54.84)"], ["G3", "22(21.78)", "28(15.05)"], ["G4", "5(4.96)", "12(6.45)"], ["unknow", "0(0.00)", "0(0.00)"], ["AJCC stage", "", ""], ["I", "66(64.35)", "102(54.54)"], ["II", "10(9.90)", "36(19.36)"], ["III", "13(12.87)", "24(12.90)"], ["IV", "12(11.88)", "24(12.90)"], ["unknow", "0(0.00)", "0(0.00)"], ["T stage", "", ""], ["T1", "68(67.33)", "110(59.14)"], ["T2", "11(10.89)", "42(22.58)"], ["T3", "21(20.79)", "25(13.44)"], ["T4", "1(0.99)", "9(4.84)"], ["N stage", "", ""], ["N0", "11(90.10)", "176(94.62)"], ["N1-3", "10(9.90)", "10(5.38)"], ["unknow", "0(0.00)", "0(0.00)"], ["M stage", "", ""], ["M0", "94(93.07)", "171(91.94)"], ["M1", "7(6.93)", "15(8.06)"], ["unknow", "0(0.00)", "0(0.00)"]], "row_count": 33, "column_count": 3, "numeric_cells": 53, "header_rows": 2, "locator": "section[3]/table-wrap[2]#d31e581"}}], "gaps": ["asset:data:geo:E-MTAB-1980 not downloaded", "asset:data:geo:E-MTAB-1980 licence not read"]}, "analysis": {"state": "partial", "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": "Kaplan-Meier analysis was used to evaluate OS, and the log-rank test was used to compare the OS between groups."}}, {"id": "method-2", "family": "group_comparison", "specific": "mann_whitney", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_mann_whitney"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Mann-Whitney"}}, {"id": "method-3", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-4", "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 regression"}}, {"id": "method-5", "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-6", "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": "PCA"}}, {"id": "method-7", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC analysis"}}], "targets": [], "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": ["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": ["E-MTAB-1980"], "resolved_accessions": ["E-MTAB-1980"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: TCGA (https://tcga-data.nci.nih.gov/tcga/), ArrayExpress (https://www.ebi.ac.uk/arrayexpress/), TIMER (https://cistrome.shinyapps.io/timer/), and GDSC (https://www.cancerrxgene.org/) websites."], "basis": "The paper names E-MTAB-1980 in ArrayExpress 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:34568046", "data:geo:E-MTAB-1980", "asset:table:pmid:34568046:1", "asset:table:pmid:34568046:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:E-MTAB-1980"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:35:16Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 37440, "completion_tokens": 3248, "cached_tokens": 792}}, "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:34568046", "type": "paper", "label": "pmid:34568046"}, {"id": "source:pmid:34568046", "type": "manuscript", "label": "PMID 34568046 full text"}, {"id": "data:geo:E-MTAB-1980", "type": "dataset", "label": "GEO E-MTAB-1980"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34568046", "type": "paper", "label": "pmid:34568046"}, {"id": "source:pmid:34568046", "type": "manuscript", "label": "PMID 34568046 full text"}, {"id": "data:geo:E-MTAB-1980", "type": "dataset", "label": "GEO E-MTAB-1980"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34568046", "type": "extraction", "used": ["source:pmid:34568046"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-E-MTAB-1980", "type": "accession_resolution", "used": ["data:geo:E-MTAB-1980"], "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:34568046", "parent_hash": "sha256:dfdca111a069d6318c5680761fa57841adfec80fe22d0453f902d0234dd1fa75", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:E-MTAB-1980 licence not read", "asset:data:geo:E-MTAB-1980 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": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ta, PID gene sets, including the cell cycle, caspase pathway, Myc pathway were also related to th"], "order_basis": "paper_text_order:7346", "id": "assay:1"}, {"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": ["Kaplan-Meier analysis was used to evaluate OS, and the log-rank test was used to compare the OS between groups."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}