Complement and coagulation cascades are associated with prognosis and the immune microenvironment of lower-grade glioma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38410234", "kind": "science-record", "revision": 4, "content_hash": "sha256:041f8ce5f35418058c5f4e153da30a9fa1db60ef619cf6a1c2d999b0538a73a2", "created_at": "2026-11-01T19:20:21Z", "updated_at": "2026-11-01T22:53:46Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Complement and coagulation cascades are associated with prognosis and the immune microenvironment of lower-grade glioma.", "doi": "10.21037/tcr-23-906", "pmid": "38410234", "authors": ["Jianmei Yang", "Lei Shen", "Jingyi Yang", "Yinzong Qu", "Chengxian Gong", "Fang Zhou", "Yuhan Liu", "Ming Luo", "Li Zhao"], "journal": "Translational cancer research", "year": 2024, "abstract": "Background: Abnormal coagulation is a common feature of glioma. There is a strong correlation between coagulation and the complement system, named complement and coagulation cascades (CCC). However, the role of CCC genes in lower-grade glioma (LGG) remains unclear. This study aimed to investigate the role of CCC genes in LGG.\nMethods: In total, 5,628 differential expressed genes were identified between 498 LGG tissues from The Cancer Genome Atlas (TCGA) and 207 normal brain tissues from Genotype-Tissue Expression Project (GTEx). Among them, 20 overlapped CCC genes were identified as differentially expressed CCC genes. Then, comprehensive bioinformatics analysis was used to investigate the role of CCC genes in LGG; 271 LGG tissues from the Chinese Glioma Genome Atlas (CGGA) were used as the validation dataset. Cell Counting Kit-8 (CCK8) proliferation assay, colony formation assay, and wound healing assay were conducted to explore the anti-glioma effect of the sensitive drugs we predicted.\nResults: We constructed a risk signature consisting of six CCC genes, including F2R, SERPINA1, TFPI, C1QC, C2, and C3AR1. The CCC gene-based risk signature could accurately predict the prognosis of patients with LGG. In addition, we found that the JAK-STAT, NOD-like receptor, Notch, PI3K-Akt, and Rap1 signaling pathways might be activated and had crosstalk with CCC in the high-risk group. Our findings analyses demonstrated that samples in high- and low-risk groups had different immune landscapes. Moreover, patients in the high-risk group might have greater resistance to immunotherapy. We validated the accuracy of the risk signature in predicting immunotherapy response in two public immunotherapy cohorts, GSE135222 and GSE78220. By means of oncoPredict, MG-132, BMS-536924, PLX-4720, and AZD6482 were identified as potential sensitive drugs for high-risk patients, of which MG-132 was particularly recommended for high-risk patients. We performed in vitro experiments to explore the anti-glioma effect of MG-132, and the results demonstrated MG-132 could inhibit the proliferation and migration of glioma cells.\nConclusions: Our findings show that CCC genes are associated with the prognosis and immune infiltration of LGG and provide possible immunotherapeutic and novel chemotherapeutic strategies for patients with LGG based on the risk signature.", "claims": [{"id": "claim-method", "statement": "R package “limma” was used to identify differentially expressed genes between TCGA and GTEx, and genes with logFC (Log2 foldchange) >1 and q<0.05 were considered as differentially expressed genes (27).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38410234", "locator": "sections[5] \"Identification of differentially expressed CCC genes\" paragraph 2", "quote": "R package “limma” was used to identify differentially expressed genes between TCGA and GTEx, and genes with logFC (Log2 foldchange) >1 and q<0.05 were considered as differentially expressed genes (27)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "A total of 769 patients with LGG were included in this study, 498 in TCGA, and 271 in CGGA. Among them, patients in TCGA were divided into the training set, and patients in CGGA were divided into the validation set. RNA-seq and clinical data of patients were collected from TCGA and CGGA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38410234", "locator": "sections[4] \"Data extraction\" paragraph 2", "quote": "A total of 769 patients with LGG were included in this study, 498 in TCGA, and 271 in CGGA. Among them, patients in TCGA were divided into the training set, and patients in CGGA were divided into the validation set. RNA-seq and clinical data of patients were collected from TCGA and CGGA."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In total, 5,628 differential expressed genes were identified between 498 LGG tissues from The Cancer Genome Atlas (TCGA) and 207 normal brain tissues from Genotype-Tissue Expression Project (GTEx).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38410234", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "In total, 5,628 differential expressed genes were identified between 498 LGG tissues from The Cancer Genome Atlas (TCGA) and 207 normal brain tissues from Genotype-Tissue Expression Project (GTEx)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In total, 5,628 differential expressed genes were identified between 498 LGG tissues from The Cancer Genome Atlas (TCGA) and 207 normal brain tissues from Genotype-Tissue Expression Project (GTEx).", "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:38410234"], "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. 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Cell Counting Kit-8 (CCK8) proliferation assay, colony formation assay", "re the anti-glioma effect of the MG-132. The CCK8 assay and colony formation assay demonstrate", "xplore the anti-glioma effect of MG-132. (A) CCK8 results showing MG-132 inhibited the prolife", "<0.001; ****, P<0.0001. OD, optical density; CCK8, Cell Counting Kit-8."], "order_basis": "paper_text_order:918", "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": ["e Academy of Sciences (Shanghai, China) were cultured in complete medium [Dulbecco’s modified Eagle m", "g sensitivity experiments, glioma cells were cultured in normal complete medium and complete medium c"], "order_basis": "paper_text_order:2862", "id": "assay:2"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["R package “limma” was used to identify differentially expressed genes between TCGA and GTEx, and genes with logFC (Log2 foldchange) >1 and q<0.05 were considered as differentially expressed genes (27)."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}