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pmid:34659201

Development and Validation of a Combined Glycolysis and Immune Prognostic Model for Melanoma.

Yang Yang · Yaling Li · Ruiqun Qi · Lan Zhang

Frontiers in immunology · 2021 doi:10.3389/fimmu.2021.711145

Paper

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Experiment

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Data

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Development and Validation of a Combined Glycolysis and Immune Prognostic Model for Melanoma.
doi
10.3389/fimmu.2021.711145
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34659201
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Yang Yang
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Yaling Li
[2]
Ruiqun Qi
[3]
Lan Zhang
journal
Frontiers in immunology
year
2021
abstract
Background: Glycolytic effects and immune microenvironments play important roles in the development of melanoma. However, reliable biomarkers for prognostic prediction of melanoma as based on glycolysis and immune status remain to be identified. Methods: Glycolysis-related genes (GRGs) were obtained from the Molecular Signatures database and immune-related genes (IRGs) were downloaded from the ImmPort dataset. Prognostic GRGs and IRGs in the TCGA (The Cancer Genome Atlas) and GSE65904 datasets were identified. Least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used for model construction. Glycolysis expression profiles and the infiltration of immune cells were analyzed and compared. Finally, in vitro experiments were performed to assess the expression and function of these CIGI genes. Results: Four prognostic glycolysis- and immune-related signatures (SEMA4D, IFITM1, KIF20A and GPR87) were identified for use in constructing a comprehensive glycolysis and immune (CIGI) model. CIGI proved to be a stable, predictive method as determined from different datasets and subgroups of patients and served as an independent prognostic factor for melanoma patients. In addition, patients in the high-CIGI group showed increased levels of glycolytic gene expressions and exhibited immune-suppressive features. Finally, SEMA4D and IFITM1 may function as tumor suppressor genes, while KIF20A and GPR87 may function as oncogenes in melanoma as revealed from results of in vitro experiments. Conclusion: In this report we present our findings on the development and validation of a novel prognostic classifier for use in patients with melanoma as based on glycolysis and immune expression profiles.
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Least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used for model construction.
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Four prognostic glycolysis- and immune-related signatures (SEMA4D, IFITM1, KIF20A and GPR87) were identified for use in constructing a comprehensive glycolysis and immune (CIGI) model.
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Four prognostic glycolysis- and immune-related signatures (SEMA4D, IFITM1, KIF20A and GPR87) were identified for use in constructing a comprehensive glycolysis and immune (CIGI) model.
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Four prognostic glycolysis- and immune-related signatures (SEMA4D, IFITM1, KIF20A and GPR87) were identified for use in constructing a comprehensive glycolysis and immune (CIGI) model.
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Whole-genome expression analysis of melanoma tumor biopsies from a population-based cohort.
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e 2A . As based on the optimized risk value, patients were assigned to either a high- or low-risk CIGI group. Re
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ssue samples were compared. Results from the immunohistochemistry assay revealed that SEMA4D and IFITM1 were d
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d melanoma cells (A375, A875, and MeWo). (C) IHC analysis of SEMA4D, IFITM1, KIF20A and GPR87
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and GPR87 in normal and melanoma tissue. (D) CCK8 assay. (E) Colony formation assays. Data rep
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34659201", "kind": "science-record", "revision": 4, "content_hash": "sha256:63dbb24d0a4d21c8a0f6413ab5ff6dcd4e28811c4967405ce42037574a47c221", "created_at": "2026-11-01T17:36:18Z", "updated_at": "2026-11-01T22:04:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development and Validation of a Combined Glycolysis and Immune Prognostic Model for Melanoma.", "doi": "10.3389/fimmu.2021.711145", "pmid": "34659201", "authors": ["Yang Yang", "Yaling Li", "Ruiqun Qi", "Lan Zhang"], "journal": "Frontiers in immunology", "year": 2021, "abstract": "Background: Glycolytic effects and immune microenvironments play important roles in the development of melanoma. However, reliable biomarkers for prognostic prediction of melanoma as based on glycolysis and immune status remain to be identified.\nMethods: Glycolysis-related genes (GRGs) were obtained from the Molecular Signatures database and immune-related genes (IRGs) were downloaded from the ImmPort dataset. Prognostic GRGs and IRGs in the TCGA (The Cancer Genome Atlas) and GSE65904 datasets were identified. Least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used for model construction. Glycolysis expression profiles and the infiltration of immune cells were analyzed and compared. Finally, in vitro experiments were performed to assess the expression and function of these CIGI genes.\nResults: Four prognostic glycolysis- and immune-related signatures (SEMA4D, IFITM1, KIF20A and GPR87) were identified for use in constructing a comprehensive glycolysis and immune (CIGI) model. CIGI proved to be a stable, predictive method as determined from different datasets and subgroups of patients and served as an independent prognostic factor for melanoma patients. In addition, patients in the high-CIGI group showed increased levels of glycolytic gene expressions and exhibited immune-suppressive features. Finally, SEMA4D and IFITM1 may function as tumor suppressor genes, while KIF20A and GPR87 may function as oncogenes in melanoma as revealed from results of in vitro experiments.\nConclusion: In this report we present our findings on the development and validation of a novel prognostic classifier for use in patients with melanoma as based on glycolysis and immune expression profiles.", "claims": [{"id": "claim-method", "statement": "Least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used for model construction.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34659201", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used for model construction."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA GSE65904.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34659201", "locator": "sections[29] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA GSE65904."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Four prognostic glycolysis- and immune-related signatures (SEMA4D, IFITM1, KIF20A and GPR87) were identified for use in constructing a comprehensive glycolysis and immune (CIGI) model.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34659201", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Four prognostic glycolysis- and immune-related signatures (SEMA4D, IFITM1, KIF20A and GPR87) were identified for use in constructing a comprehensive glycolysis and immune (CIGI) model."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Four prognostic glycolysis- and immune-related signatures (SEMA4D, IFITM1, KIF20A and GPR87) were identified for use in constructing a comprehensive glycolysis and immune (CIGI) model.", "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:34659201"], "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:GSE65904"], "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:GSE65904"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34659201", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2021.711145", "sha256": "sha256:ebc4460bf7604a83f3ea5a404a7679f7f9a24ecbe3a59e03213c1b92318230c5", "bytes": 44084, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2021.711145", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8517401", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE65904", "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=GSE65904", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE65904", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA GSE65904.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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As based on the optimized risk value, patients were assigned to either a high- or low-risk CIGI group. Re"], "order_basis": "paper_text_order:2549", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ssue samples were compared. Results from the immunohistochemistry assay revealed that SEMA4D and IFITM1 were d", "d melanoma cells (A375, A875, and MeWo). (C) IHC analysis of SEMA4D, IFITM1, KIF20A and GPR87"], "order_basis": "paper_text_order:5987", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["and GPR87 in normal and melanoma tissue. (D) CCK8 assay. (E) Colony formation assays. Data rep"], "order_basis": "paper_text_order:6865", "id": "assay:3"}, {"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": ["Least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used for model construction."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}