RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34736454", "kind": "science-record", "revision": 5, "content_hash": "sha256:73122c83252b58aa641ba92488bbc71a83a6407366e10c4a9011c148baf0ef37", "created_at": "2026-11-01T17:36:25Z", "updated_at": "2026-11-01T22:47:49Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression.", "doi": "10.1186/s12935-021-02277-0", "pmid": "34736454", "authors": ["Lei Wang", "Xiu-Xiu Liu", "Yu-Meng Yang", "Yan Wang", "Yuan-Yuan Song", "Shan Gao", "Lu-Yuan Li", "Zhi-Song Zhang"], "journal": "Cancer cell international", "year": 2021, "abstract": "BACKGROUND: The rhomboids are a family of multi-transmembrane proteins, many of which have been implicated in facilitating tumor progression. Little is yet known, however, about rhomboid-associated biomarkers in cancers. An analysis of such biomarkers could yield important insights into the role of the rhomboids in cancer pathology.\nMETHODS: In this study, we carried out the univariate Cox regression analysis and compared gene expression patterns of several rhomboid genes in 30 types of cancers by using The Cancer Genome Atlas (TCGA) database and the methods delineated in Gene Expression Profiling Interactive Analysis (GEPIA). We then used datasets GSE47032, GSE126964, GSE68417 and 75 paired pathological specimens to verify the influences of the rhomboid genes in cancer progression. Moreover, we carried out Weighted Gene Correlation Network Analysis (WGCNA) to investigate gene-related functions and we exploited potential correlations between rhomboid genes expression and immune cell infiltration in cancer tissues. Furthermore, we constructed gene-knockdown cancer cell lines to investigate rhomboid gene functions.\nRESULTS: We find that kidney renal clear cell carcinoma (KIRC) disease progression is affected by fluctuations in the expression of a number of the rhomboid family of genes and, more specifically, high levels of RHBDF2 gene expression are a good indicator of poor prognosis of the disease, as patients with high RHBDF2 expression levels exhibit less favorable survival rates compared to those with low RHBDF2 levels. Silencing of the RHBDF2 gene in KIRC cell lines leads to significantly diminished cell proliferation and migration; this is in good agreement with the identification of an enhanced presence of a number of cell growth and migration promoting signaling molecules in KIRC tumors. We found that, although high level of RHBDF2 correlated with increased infiltration of lymphocytes in cancer tissues, artificially overexpressed RHBDF2 led to an inhibition of the activity of the infiltrated immune cells through sustaining PD-L1 protein level. Furthermore, we show that RHBDF2 related cell migration and PD-L1 regulation were potentially mediated by EGFR signaling pathway.\nCONCLUSIONS: RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression and may serve as a critical prognostic biomarker for the disease.", "claims": [{"id": "claim-method", "statement": "For the computerized analyses, we used the data of TCGA to carry out the univariate Cox regression and survival analyses, and the log-rank test was used for the significance test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34736454", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "For the computerized analyses, we used the data of TCGA to carry out the univariate Cox regression and survival analyses, and the log-rank test was used for the significance test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data in this article were downloaded from publicly available datasets. The datasets for this study can be found in the TCGA database (https://cancergenome.nih.gov/) and GEO database (https://www.ncbi.nlm.nih.gov/gds).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34736454", "locator": "sections[31] \"notes\" paragraph 1", "quote": "Data in this article were downloaded from publicly available datasets. The datasets for this study can be found in the TCGA database (https://cancergenome.nih.gov/) and GEO database (https://www.ncbi.nlm.nih.gov/gds)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We find that kidney renal clear cell carcinoma (KIRC) disease progression is affected by fluctuations in the expression of a number of the rhomboid family of genes and, more specifically, high levels of RHBDF2 gene expression are a good indicator of poor prognosis of the disease, as patients with high RHBDF2 expression levels exhibit less favorable survival rates compared to those with low RHBDF2 levels.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34736454", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We find that kidney renal clear cell carcinoma (KIRC) disease progression is affected by fluctuations in the expression of a number of the rhomboid family of genes and, more specifically, high levels of RHBDF2 gene expression are a good indicator of poor prognosis of the disease, as patients with high RHBDF2 expression levels exhibit less favorable survival rates compared to those with low RHBDF2 levels."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We find that kidney renal clear cell carcinoma (KIRC) disease progression is affected by fluctuations in the expression of a number of the rhomboid family of genes and, more specifically, high levels of RHBDF2 gene expression are a good indicator of poor prognosis of the disease, as patients with high RHBDF2 expression levels exhibit less favorable survival rates compared to those with low RHBDF2 levels.", "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:34736454"], "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:GSE126964"], "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:GSE126964"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34736454", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12935-021-02277-0", "sha256": "sha256:247055bbba7e6a7f3b5eec4514c727b92d00da9d5184a5f7861471760f1947c8", "bytes": 42025, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12935-021-02277-0", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8567583", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE126964", "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=GSE126964", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE126964", "version": null, "note": "Data in this article were downloaded from publicly available datasets. The datasets for this study can be found in the TCGA database (https://cancergenome.nih.gov/) and GEO database (https://www.ncbi.nlm.nih.gov/gds).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data in this article were downloaded from publicly available datasets. The datasets for this study can be found in the TCGA database (https://cancergenome.nih.gov/) and GEO database (https://www.ncbi.nlm.nih.gov/gds).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3619137", "GSM3619138", "GSM3619139", "GSM3619140", "GSM3619141", "GSM3619142", "GSM3619143", "GSM3619144", "GSM3619145", "GSM3619146", "GSM3619147", "GSM3619148", "GSM3619149", "GSM3619150", "GSM3619151", "GSM3619152", "GSM3619153", "GSM3619154", "GSM3619155", "GSM3619156", "GSM3619157", "GSM3619158", "GSM3619159", "GSM3619160", "GSM3619161", "GSM3619162", "GSM3619163", "GSM3619164", "GSM3619165", "GSM3619166", "GSM3619167", "GSM3619168", "GSM3619169", "GSM3619170", "GSM3619171", "GSM3619172", "GSM3619173", "GSM3619174", "GSM3619175", "GSM3619176", "GSM3619177", "GSM3619178", "GSM3619179", "GSM3619180", "GSM3619181", "GSM3619182", "GSM3619183", "GSM3619184", "GSM3619185", "GSM3619186", "GSM3619187", "GSM3619188", "GSM3619189", "GSM3619190", "GSM3619191", "GSM3619192", "GSM3619193", "GSM3619194", "GSM3619195", "GSM3619196", "GSM3619197", "GSM3619198", "GSM3619199", "GSM3619200", "GSM3619201", "GSM3619202"], "sample_count": 66, "group_sizes": null, "group_sizes_basis": null, "platform": "20795", "taxon": "Homo sapiens", "title": "Genomic characterization of Chinese clear cell renal cell carcinoma", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE167093", "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=GSE167093", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE167093", "version": null, "note": "Data in this article were downloaded from publicly available datasets. The datasets for this study can be found in the TCGA database (https://cancergenome.nih.gov/) and GEO database (https://www.ncbi.nlm.nih.gov/gds).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data in this article were downloaded from publicly available datasets. The datasets for this study can be found in the TCGA database (https://cancergenome.nih.gov/) and GEO database (https://www.ncbi.nlm.nih.gov/gds).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM5092664", "GSM5092665", "GSM5092666", "GSM5092667", "GSM5092668", "GSM5092669", "GSM5092670", "GSM5092671", "GSM5092672", "GSM5092673", "GSM5092674", "GSM5092675", "GSM5092676", "GSM5092677", "GSM5092678", "GSM5092679", "GSM5092680", "GSM5092681", "GSM5092682", "GSM5092683", "GSM5092684", "GSM5092685", "GSM5092686", "GSM5092687", "GSM5092688", "GSM5092689", "GSM5092690", "GSM5092691", "GSM5092692", "GSM5092693", "GSM5092694", "GSM5092695", "GSM5092696", "GSM5092697", "GSM5092698", "GSM5092699", "GSM5092700", "GSM5092701", "GSM5092702", "GSM5092703", "GSM5092704", "GSM5092705", "GSM5092706", "GSM5092707", "GSM5092708", "GSM5092709", "GSM5092710", "GSM5092711", "GSM5092712", "GSM5092713", "GSM5092714", "GSM5092715", "GSM5092716", "GSM5092717", "GSM5092718", "GSM5092719", "GSM5092720", "GSM5092721", "GSM5092722", "GSM5092723", "GSM5092724", "GSM5092725", "GSM5092726", "GSM5092727", "GSM5092728", "GSM5092729", "GSM5092730", "GSM5092731", "GSM5092732", "GSM5092733", "GSM5092734", "GSM5092735", "GSM5092736", "GSM5092737", "GSM5092738", "GSM5092739", "GSM5092740", "GSM5092741", "GSM5092742", "GSM5092743", "GSM5092744", "GSM5092745", "GSM5092746", "GSM5092747", "GSM5092748", "GSM5092749", "GSM5092750", "GSM5092751", "GSM5092752", "GSM5092753", "GSM5092754", "GSM5092755", "GSM5092756", "GSM5092757", "GSM5092758", "GSM5092759", "GSM5092760", "GSM5092761", "GSM5092762", "GSM5092763", "GSM5092764", "GSM5092765", "GSM5092766", "GSM5092767", "GSM5092768", "GSM5092769", "GSM5092770", "GSM5092771", "GSM5092772", "GSM5092773", "GSM5092774", "GSM5092775", "GSM5092776", "GSM5092777", "GSM5092778", "GSM5092779", "GSM5092780", "GSM5092781", "GSM5092782", "GSM5092783", "GSM5092784", "GSM5092785", "GSM5092786", "GSM5092787", "GSM5092788", "GSM5092789", "GSM5092790", "GSM5092791", "GSM5092792", "GSM5092793", "GSM5092794", "GSM5092795", "GSM5092796", "GSM5092797", "GSM5092798", "GSM5092799", "GSM5092800", "GSM5092801", "GSM5092802", "GSM5092803", "GSM5092804", "GSM5092805", "GSM5092806", "GSM5092807", "GSM5092808", "GSM5092809", "GSM5092810", "GSM5092811", "GSM5092812", "GSM5092813", "GSM5092814", "GSM5092815", "GSM5092816", "GSM5092817", "GSM5092818", "GSM5092819", "GSM5092820", "GSM5092821", "GSM5092822", "GSM5092823", "GSM5092824", "GSM5092825", "GSM5092826", "GSM5092827", "GSM5092828", "GSM5092829", "GSM5092830", "GSM5092831", "GSM5092832", "GSM5092833", "GSM5092834", "GSM5092835", "GSM5092836", "GSM5092837", "GSM5092838", "GSM5092839", "GSM5092840", "GSM5092841", "GSM5092842", "GSM5092843", "GSM5092844", "GSM5092845", "GSM5092846", "GSM5092847", "GSM5092848", "GSM5092849", "GSM5092850", "GSM5092851", "GSM5092852", "GSM5092853", "GSM5092854", "GSM5092855", "GSM5092856", "GSM5092857", "GSM5092858", "GSM5092859", "GSM5092860", "GSM5092861", "GSM5092862", "GSM5092863", "GSM5092864", "GSM5092865", "GSM5092866", "GSM5092867", "GSM5092868", "GSM5092869", "GSM5092870", "GSM5092871", "GSM5092872", "GSM5092873", "GSM5092874", "GSM5092875", "GSM5092876", "GSM5092877", "GSM5092878", "GSM5092879", "GSM5092880", "GSM5092881", "GSM5092882", "GSM5092883", "GSM5092884", "GSM5092885", "GSM5092886", "GSM5092887", "GSM5092888", "GSM5092889", "GSM5092890", "GSM5092891", "GSM5092892", "GSM5092893", "GSM5092894", "GSM5092895", "GSM5092896", "GSM5092897", "GSM5092898", "GSM5092899", "GSM5092900", "GSM5092901", "GSM5092902", "GSM5092903", "GSM5092904", "GSM5092905", "GSM5092906", "GSM5092907", "GSM5092908", "GSM5092909", "GSM5092910", "GSM5092911", "GSM5092912", "GSM5092913", "GSM5092914", "GSM5092915", "GSM5092916", "GSM5092917", "GSM5092918", "GSM5092919", "GSM5092920", "GSM5092921", "GSM5092922", "GSM5092923", "GSM5092924", "GSM5092925", "GSM5092926", "GSM5092927", "GSM5092928", "GSM5092929", "GSM5092930", "GSM5092931", "GSM5092932", "GSM5092933", "GSM5092934", "GSM5092935", "GSM5092936", "GSM5092937", "GSM5092938", "GSM5092939", "GSM5092940", "GSM5092941", "GSM5092942", "GSM5092943", "GSM5092944", "GSM5092945", "GSM5092946", "GSM5092947", "GSM5092948", "GSM5092949", "GSM5092950", "GSM5092951", "GSM5092952", "GSM5092953", "GSM5092954", "GSM5092955", "GSM5092956", "GSM5092957", "GSM5092958", "GSM5092959", "GSM5092960", "GSM5092961", "GSM5092962", "GSM5092963", "GSM5092964", "GSM5092965", "GSM5092966", "GSM5092967", "GSM5092968", "GSM5092969", "GSM5092970", "GSM5092971", "GSM5092972", "GSM5092973", "GSM5092974", "GSM5092975", "GSM5092976", "GSM5092977", "GSM5092978", "GSM5092979", "GSM5092980", "GSM5092981", "GSM5092982", "GSM5092983", "GSM5092984", "GSM5092985", "GSM5092986", "GSM5092987", "GSM5092988", "GSM5092989", "GSM5092990", "GSM5092991", "GSM5092992", "GSM5092993", "GSM5092994", "GSM5092995", "GSM5092996", "GSM5092997", "GSM5092998", "GSM5092999", "GSM5093000", "GSM5093001", "GSM5093002", "GSM5093003", "GSM5093004", "GSM5093005", "GSM5093006", "GSM5093007", "GSM5093008", "GSM5093009", "GSM5093010", "GSM5093011", "GSM5093012", "GSM5093013", "GSM5093014", "GSM5093015", "GSM5093016", "GSM5093017", "GSM5093018", "GSM5093019", "GSM5093020", "GSM5093021", "GSM5093022", "GSM5093023", "GSM5093024", "GSM5093025", "GSM5093026", "GSM5093027", "GSM5093028", "GSM5093029", "GSM5093030", "GSM5093031", "GSM5093032", "GSM5093033", "GSM5093034", "GSM5093035", "GSM5093036", "GSM5093037", "GSM5093038", "GSM5093039", "GSM5093040", "GSM5093041", "GSM5093042", "GSM5093043", "GSM5093044", "GSM5093045", "GSM5093046", "GSM5093047", "GSM5093048", "GSM5093049", "GSM5093050", "GSM5093051", "GSM5093052", "GSM5093053", "GSM5093054", "GSM5093055", "GSM5093056", "GSM5093057", "GSM5093058", "GSM5093059", "GSM5093060", "GSM5093061", "GSM5093062", "GSM5093063", "GSM5093064", "GSM5093065", "GSM5093066", "GSM5093067", "GSM5093068", "GSM5093069", "GSM5093070", "GSM5093071", "GSM5093072", "GSM5093073", "GSM5093074", "GSM5093075", "GSM5093076", "GSM5093077", "GSM5093078", "GSM5093079", "GSM5093080", "GSM5093081", "GSM5093082", "GSM5093083", "GSM5093084", "GSM5093085", "GSM5093086", "GSM5093087", "GSM5093088", "GSM5093089", "GSM5093090", "GSM5093091", "GSM5093092", "GSM5093093", "GSM5093094", "GSM5093095", "GSM5093096", "GSM5093097", "GSM5093098", "GSM5093099", "GSM5093100", "GSM5093101", "GSM5093102", "GSM5093103", "GSM5093104", "GSM5093105", "GSM5093106", "GSM5093107", "GSM5093108", "GSM5093109", "GSM5093110", "GSM5093111", "GSM5093112", "GSM5093113", "GSM5093114", "GSM5093115", "GSM5093116", "GSM5093117", "GSM5093118", "GSM5093119", "GSM5093120", "GSM5093121", "GSM5093122", "GSM5093123", "GSM5093124", "GSM5093125", "GSM5093126", "GSM5093127", "GSM5093128", "GSM5093129", "GSM5093130", "GSM5093131", "GSM5093132", "GSM5093133", "GSM5093134", "GSM5093135", "GSM5093136", "GSM5093137", "GSM5093138", "GSM5093139", "GSM5093140", "GSM5093141", "GSM5093142", "GSM5093143", "GSM5093144", "GSM5093145", "GSM5093146", "GSM5093147", "GSM5093148", "GSM5093149", "GSM5093150", "GSM5093151", "GSM5093152", "GSM5093153", "GSM5093154", "GSM5093155", "GSM5093156", "GSM5093157", "GSM5093158", "GSM5093159", "GSM5093160", "GSM5093161", "GSM5093162", "GSM5093163", "GSM5093164", "GSM5093165", "GSM5093166", "GSM5093167", "GSM5093168", "GSM5093169", "GSM5093170", "GSM5093171", "GSM5093172", "GSM5093173", "GSM5093174", "GSM5093175", "GSM5093176", "GSM5093177", "GSM5093178", "GSM5093179", "GSM5093180", "GSM5093181", "GSM5093182", "GSM5093183", "GSM5093184", "GSM5093185", "GSM5093186", "GSM5093187", "GSM5093188", "GSM5093189", "GSM5093190", "GSM5093191", "GSM5093192", "GSM5093193", "GSM5093194", "GSM5093195", "GSM5093196", "GSM5093197", "GSM5093198", "GSM5093199", "GSM5093200", "GSM5093201", "GSM5093202", "GSM5093203", "GSM5093204", "GSM5093205", "GSM5093206", "GSM5093207", "GSM5093208", "GSM5093209", "GSM5093210", "GSM5093211", "GSM5093212", "GSM5093213", "GSM5093214", "GSM5093215", "GSM5093216", "GSM5093217", "GSM5093218", "GSM5093219", "GSM5093220", "GSM5093221", "GSM5093222", "GSM5093223", "GSM5093224", "GSM5093225", "GSM5093226", "GSM5093227", "GSM5093228", "GSM5093229", "GSM5093230", "GSM5093231", "GSM5093232", "GSM5093233", "GSM5093234", "GSM5093235", "GSM5093236", "GSM5093237", "GSM5093238", "GSM5093239", "GSM5093240", "GSM5093241", "GSM5093242", "GSM5093243", "GSM5093244", "GSM5093245", "GSM5093246", "GSM5093247", "GSM5093248", "GSM5093249", "GSM5093250", "GSM5093251", "GSM5093252", "GSM5093253", "GSM5093254", "GSM5093255", "GSM5093256", "GSM5093257", "GSM5093258", "GSM5093259", "GSM5093260", "GSM5093261", "GSM5093262", "GSM5093263", "GSM5093264", "GSM5093265", "GSM5093266", "GSM5093267", "GSM5093268", "GSM5093269", "GSM5093270", "GSM5093271", "GSM5093272", "GSM5093273", "GSM5093274", "GSM5093275", "GSM5093276", "GSM5093277", "GSM5093278", "GSM5093279", "GSM5093280", "GSM5093281", "GSM5093282", "GSM5093283", "GSM5093284", "GSM5093285", "GSM5093286", "GSM5093287", "GSM5093288", "GSM5093289", "GSM5093290", "GSM5093291", "GSM5093292", "GSM5093293", "GSM5093294", "GSM5093295", "GSM5093296", "GSM5093297", "GSM5093298", "GSM5093299", "GSM5093300", "GSM5093301", "GSM5093302", "GSM5093303", "GSM5093304", "GSM5093305", "GSM5093306", "GSM5093307", "GSM5093308", "GSM5093309", "GSM5093310", "GSM5093311", "GSM5093312", "GSM5093313", "GSM5093314", "GSM5093315", "GSM5093316", "GSM5093317", "GSM5093318", "GSM5093319"], "sample_count": 656, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Sexual dimorphism in cancer: insights from transcriptional signatures in kidney tissues and renal cell carcinoma", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE47032", "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=GSE47032", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE47032", "version": null, "note": "Data in this article were downloaded from publicly available datasets. The datasets for this study can be found in the TCGA database (https://cancergenome.nih.gov/) and GEO database (https://www.ncbi.nlm.nih.gov/gds).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data in this article were downloaded from publicly available datasets. The datasets for this study can be found in the TCGA database (https://cancergenome.nih.gov/) and GEO database (https://www.ncbi.nlm.nih.gov/gds).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1143384", "GSM1143385", "GSM1143386", "GSM1143387", "GSM1143388", "GSM1143389", "GSM1143390", "GSM1143391", "GSM1143392", "GSM1143393", "GSM1143394", "GSM1143395", "GSM1143396", "GSM1143397", "GSM1143398", "GSM1143399", "GSM1143400", "GSM1143401", "GSM1143402", "GSM1143403", "GSM1143404", "GSM1143405", "GSM1143406", "GSM1143407", "GSM1143408", "GSM1143409", "GSM1143410", "GSM1143411", "GSM1143412", "GSM1143413", "GSM1143414", "GSM1143415", "GSM1143416", "GSM1143417", "GSM1143418", "GSM1143419", "GSM1143420", "GSM1143421", "GSM1143422", "GSM1143423"], "sample_count": 40, "group_sizes": null, "group_sizes_basis": null, "platform": "5188;5175", "taxon": "Homo sapiens", "title": "Genome-wide analysis of differentially expressed genes and splicing isoforms in clear cell Renal Cell Carcinoma", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE68417", "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=GSE68417", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE68417", "version": null, "note": "Data in this article were downloaded from publicly available datasets. The datasets for this study can be found in the TCGA database (https://cancergenome.nih.gov/) and GEO database (https://www.ncbi.nlm.nih.gov/gds).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data in this article were downloaded from publicly available datasets. The datasets for this study can be found in the TCGA database (https://cancergenome.nih.gov/) and GEO database (https://www.ncbi.nlm.nih.gov/gds).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1671350", "GSM1671351", "GSM1671352", "GSM1671353", "GSM1671354", "GSM1671355", "GSM1671356", "GSM1671357", "GSM1671358", "GSM1671359", "GSM1671360", "GSM1671361", "GSM1671362", "GSM1671363", "GSM1671364", "GSM1671365", "GSM1671366", "GSM1671367", "GSM1671368", "GSM1671369", "GSM1671370", "GSM1671371", "GSM1671372", "GSM1671373", "GSM1671374", "GSM1671375", "GSM1671376", "GSM1671377", "GSM1671378", "GSM1671379", "GSM1671380", "GSM1671381", "GSM1671382", "GSM1671383", "GSM1671384", "GSM1671385", "GSM1671386", "GSM1671387", "GSM1671388", "GSM1671389", "GSM1671390", "GSM1671391", "GSM1671392", "GSM1671393", "GSM1671394", "GSM1671395", "GSM1671396", "GSM1671397", "GSM1671398"], "sample_count": 49, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Gene expression characterization of high and low grade clear cell renal cell carcinoma", "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:GSE126964 not downloaded", "asset:data:geo:GSE126964 licence not read", "asset:data:geo:GSE167093 not downloaded", "asset:data:geo:GSE167093 licence not read", "asset:data:geo:GSE47032 not downloaded", "asset:data:geo:GSE47032 licence not read", "asset:data:geo:GSE68417 not downloaded", "asset:data:geo:GSE68417 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": "For the computerized analyses, we used the data of TCGA to carry out the univariate Cox regression and survival analyses, and the log-rank test was used for the significance test."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "student t-test"}}, {"id": "method-3", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"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": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson correlation"}}], "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": ["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": ["GSE68417", "GSE126964", "GSE47032", "GSE167093"], "resolved_accessions": ["GSE68417", "GSE126964", "GSE47032", "GSE167093"], "statements": ["Data in this article were downloaded from publicly available datasets. The datasets for this study can be found in the TCGA database (https://cancergenome.nih.gov/) and GEO database (https://www.ncbi.nlm.nih.gov/gds)."], "basis": "The paper names GSE68417, GSE126964, GSE47032, GSE167093 in Gene Expression Omnibus (GEO) databases 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:34736454", "data:geo:GSE126964"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE126964"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:06:10Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12089, "completion_tokens": 2359, "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:34736454", "type": "paper", "label": "pmid:34736454"}, {"id": "source:pmid:34736454", "type": "manuscript", "label": "PMID 34736454 full text"}, {"id": "data:geo:GSE126964", "type": "dataset", "label": "GEO GSE126964"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34736454", "type": "paper", "label": "pmid:34736454"}, {"id": "source:pmid:34736454", "type": "manuscript", "label": "PMID 34736454 full text"}, {"id": "data:geo:GSE126964", "type": "dataset", "label": "GEO GSE126964"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34736454", "type": "extraction", "used": ["source:pmid:34736454"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE126964", "type": "accession_resolution", "used": ["data:geo:GSE126964"], "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:34736454", "parent_hash": "sha256:8b0db3ea7a6829303ac217be8669dea7a153825158e70a25e4e6f452300c4c13", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE126964 licence not read", "asset:data:geo:GSE126964 not downloaded", "asset:data:geo:GSE167093 licence not read", "asset:data:geo:GSE167093 not downloaded", "asset:data:geo:GSE47032 licence not read", "asset:data:geo:GSE47032 not downloaded", "asset:data:geo:GSE68417 licence not read", "asset:data:geo:GSE68417 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": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["er tissues. Furthermore, we constructed gene-knockdown cancer cell lines to investigate rhomboid ge"], "order_basis": "paper_text_order:1110", "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": 0.77, "evidence": ["f Sciences (Shanghai, China). The cells were cultured in RPMI1640 medium supplemented with 10% FBS. T"], "order_basis": "paper_text_order:2594", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["body (Proteintech, #23181-1-AP) was used for immunohistochemical staining and Western blotting. PD-L1 antibod"], "order_basis": "paper_text_order:2870", "id": "assay:3"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["as used for immunohistochemical staining and Western blotting. PD-L1 antibody (Boster, #BA1683-2), EGFR an", "FR antibody (Boster, #BM-4676) were used for Western blotting. BeyoClick™ EdU Cell Proliferation Kit with"], "order_basis": "paper_text_order:2903", "id": "assay:4"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ltraSYBR mixture (CWBIO, CW0957M) was use to real-time quantitative PCR. Matrigel (Corning #354248) was used to buil"], "order_basis": "paper_text_order:3486", "id": "assay:5"}, {"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": ["For the computerized analyses, we used the data of TCGA to carry out the univariate Cox regression and survival analyses, and the log-rank test was used for the significance test."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}