CD44-Mediated Poor Prognosis in Glioma Is Associated With M2-Polarization of Tumor-Associated Macrophages and Immunosuppression.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35187044", "kind": "science-record", "revision": 5, "content_hash": "sha256:38ef21178018406a53c57c7d197b1d577c3e2aa66ea6dbe03585fbbd3fc5f2f3", "created_at": "2026-11-01T17:36:57Z", "updated_at": "2026-11-01T22:48:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "CD44-Mediated Poor Prognosis in Glioma Is Associated With M2-Polarization of Tumor-Associated Macrophages and Immunosuppression.", "doi": "10.3389/fsurg.2021.775194", "pmid": "35187044", "authors": ["Yong Xiao", "Kun Yang", "Zhen Wang", "Mengjie Zhao", "Yanxiang Deng", "Wei Ji", "Yuanjie Zou", "Chunfa Qian", "Yong Liu", "Hong Xiao", "Hongyi Liu"], "journal": "Frontiers in surgery", "year": 2021, "abstract": "BACKGROUND: Glioma is the most common primary brain tumor with a poor prognosis. Key genes that are negatively related to prognosis may provide the therapy targets to cure glioma. To clarify the role of CD44 in glioma, we explored its function at bulk-transcriptome, spatial and single-cell transcriptome levels.\nMETHODS: In total, expression profiles with survival data of whole-grade glioma from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), RNA-seq data with anatomic information of glioblastoma (GBM) from the Ivy Glioblastoma Atlas Project, RNA-sequencing (RNA-seq) data from recurrent GBM receiving adjuvant anti-PD-1 immunotherapy accessed through GSE121810, and single-cell RNA-seq data of GBM under accession GSE103224 were enrolled in this study. CD44-specific findings were further analyzed by R language.\nRESULTS: CD44 is positively correlated with WHO grade of malignancy and is negatively related to prognosis in glioma. Meanwhile, CD44 predominantly expresses in GBM mesenchymal subtype, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses reveal that CD44 positively coexpressed genes are closely related to glioma immunity. Moreover, CD44+ cells mainly distribute in perinecrotic region with high expression of immune factors. At single-cell resolution, only malignant tumor cells, tumor-associated macrophages (TAMs), and T cells express CD44 in GBM. CD44+ malignant tumor cells are in mesenchymal-1-like (MES1-like) cellular state, and CD44+ TAMs are in M2 phenotype. CD44+ T cells have high expression of both PD-1 and PD-L1. CD44 and its directly interacted inhibitory immunomodulators are upregulated in patients with nonresponder recurrent GBM treated with PD-1 blockade therapy.\nCONCLUSION: Our work demonstrates that CD44, a new M2 TAM biomarker, is involved in immune suppressor and promote glioma progression in glioma microenvironment. These results expand our understanding of CD44-specific clinical and immune features in glioma.", "claims": [{"id": "claim-method", "statement": "Survival curves were performed by Kaplan–Meier analysis between CD44 higher and lower group and were tested for significance using the Mantel–Cox log-rank test. Hazard ratio (HR) and confidence interval (CI) were also computed to confirm the prognostic value of CD44 in patients with glioma. Furthermore, Cox proportional hazards model, including patients' age and gender, was used to evaluate the predictor effect of CD44.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35187044", "locator": "sections[4] \"Survival Analysis\" paragraph 2", "quote": "Survival curves were performed by Kaplan–Meier analysis between CD44 higher and lower group and were tested for significance using the Mantel–Cox log-rank test. Hazard ratio (HR) and confidence interval (CI) were also computed to confirm the prognostic value of CD44 in patients with glioma. Furthermore, Cox proportional hazards model, including patients' age and gender, was used to evaluate the predictor effect of CD44."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. These data can be found at: TCGA database (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga), the CGGA database (http://www.cgga.org.cn/), the IGAP database (http://glioblastoma.alleninstitute.org/), and the GEO database (https://www.ncbi.nlm.nih.gov/geo) with accession number GSE121810 and GSE103224.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35187044", "locator": "sections[23] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. These data can be found at: TCGA database (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga), the CGGA database (http://www.cgga.org.cn/), the IGAP database (http://glioblastoma.alleninstitute.org/), and the GEO database (https://www.ncbi.nlm.nih.gov/geo) with accession number GSE121810 and GSE103224."}], "state": "complete"}, {"id": "claim-target-result", "statement": "CD44 is positively correlated with WHO grade of malignancy and is negatively related to prognosis in glioma.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35187044", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "CD44 is positively correlated with WHO grade of malignancy and is negatively related to prognosis in glioma."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "CD44 is positively correlated with WHO grade of malignancy and is negatively related to prognosis in glioma.", "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:35187044"], "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:GSE103224"], "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:GSE103224"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35187044", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fsurg.2021.775194", "sha256": "sha256:2ee89a08127301e2c85f5696c6b16f069d5a43598185f6335ba60d2e1e6c46b2", "bytes": 63509, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fsurg.2021.775194", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8850306", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE103224", "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=GSE103224", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE103224", "version": null, "note": "Publicly available datasets were analyzed in this study. 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These data can be found at: TCGA database (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga), the CGGA database (http://www.cgga.org.cn/), the IGAP database (http://glioblastoma.alleninstitute.org/), and the GEO database (https://www.ncbi.nlm.nih.gov/geo) with accession number GSE121810 and GSE103224.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. These data can be found at: TCGA database (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga), the CGGA database (http://www.cgga.org.cn/), the IGAP database (http://glioblastoma.alleninstitute.org/), and the GEO database (https://www.ncbi.nlm.nih.gov/geo) with accession number GSE121810 and GSE103224.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3447008", "GSM3447009", "GSM3447010", "GSM3447011", "GSM3447012", "GSM3447013", "GSM3447014", "GSM3447015", "GSM3447016", "GSM3447017", "GSM3447018", "GSM3447019", "GSM3447020", "GSM3447021", "GSM3447022", "GSM3447023", "GSM3447024", "GSM3447025", "GSM3447026", "GSM3447027", "GSM3447028", "GSM3447029", "GSM3447030", "GSM3447031", "GSM3447032", "GSM3447033", "GSM3447034", "GSM3447035", "GSM3447036"], "sample_count": 29, "group_sizes": null, "group_sizes_basis": null, "platform": "21290", "taxon": "Homo sapiens", "title": "Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma", "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:GSE103224 not downloaded", "asset:data:geo:GSE103224 licence not read", "asset:data:geo:GSE121810 not downloaded", "asset:data:geo:GSE121810 licence not read"]}, "analysis": {"state": "complete", "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": "Survival curves were performed by Kaplan–Meier analysis between CD44 higher and lower group and were tested for significance using the Mantel–Cox log-rank test. 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Hazard ratio (HR) and confidence interval (CI) were also computed to confirm the prognostic value of CD44 in patients with glioma. Furthermore, Cox proportional hazards model, including patients' age and gender, was used to evaluate the predictor effect of CD44."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}