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pmid:33215029

Using Machine Learning Modeling to Explore New Immune-Related Prognostic Markers in Non-Small Cell Lung Cancer.

Jiasheng Xu · Han Nie · Jiarui He · Xinlu Wang · Kaili Liao · Luxia Tu · Zhenfang Xiong

Frontiers in oncology · 2020 doi:10.3389/fonc.2020.550002

Paper

complete

Experiment

complete

Data

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Analysis

complete

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title
Using Machine Learning Modeling to Explore New Immune-Related Prognostic Markers in Non-Small Cell Lung Cancer.
doi
10.3389/fonc.2020.550002
pmid
33215029
authors array · 7 items
[0]
Jiasheng Xu
[1]
Han Nie
[2]
Jiarui He
[3]
Xinlu Wang
[4]
Kaili Liao
[5]
Luxia Tu
[6]
Zhenfang Xiong
journal
Frontiers in oncology
year
2020
abstract
OBJECTIVE: To find new immune-related prognostic markers for non-small cell lung cancer (NSCLC). METHODS: We found GSE14814 is related to NSCLC in GEO database. The non-small cell lung cancer observation (NSCLC-OBS) group was evaluated for immunity and divided into high and low groups for differential gene screening according to the score of immune evaluation. A single factor COX regression analysis was performed to select the genes related to prognosis. A prognostic model was constructed by machine learning, and test whether the model has a test efficacy for prognosis. A chip-in-chip non-small cell lung cancer chemotherapy (NSCLC-ACT) sample was used as a validation dataset for the same validation and prognostic analysis of the model. The coexpression genes of hub genes were obtained by pearson analysis and gene enrichment, function enrichment and protein interaction analysis. The tumor samples of patients with different clinical stages were detected by immunohistochemistry and the expression difference of prognostic genes in tumor tissues of patients with different stages was compared. RESULTS: By screening, we found that LYN, C3, COPG2IT1, HLA.DQA1, and TNFRSF17 is closely related to prognosis. After machine learning, we constructed the immune prognosis model from these 5 genes, and the model AUC values were greater than 0.9 at three time periods of 1, 3, and 5 years; the total survival period of the low-risk group was significantly better than that of the high-risk group. The results of prognosis analysis in ACT samples were consistent with OBS groups. The coexpression genes are mainly involved B cell receptor signaling pathway and are mainly enriched in apoptotic cell clearance. Prognostic key genes are highly correlated with PDCD1, PDCD1LG2, LAG3, and CTLA4 immune checkpoints. The immunohistochemical results showed that the expression of COPG2IT1 and HLA.DQA1 in stage III increased significantly and the expression of LYN, C3, and TNFRSF17 in stage III decreased significantly compared with that of stage I. The experimental results are consistent with the previous analysis. CONCLUSION: LYN, C3, COPG2IT1, LA.DQA1, and NFRSF17 may be new immune markers to judge the prognosis of patients with non-small cell lung cancer.
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title
Prognostic and Predictive Gene Signature for Adjuvant Chemotherapy in Resected Non-Small-Cell Lung Cancer
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Experimental Verification of Prognostic Genes
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Basic information of patients in the stage I lung cancer group and stage III lung cancer group.
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Experimental Verification of Prognostic Related Genes
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h different clinical stages were detected by immunohistochemistry and the expression difference of prognostic
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LG2, LAG3, and CTLA4 immune checkpoints. The immunohistochemical results showed that the expression of COPG2I
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tients are shown in Table 2 . The results of immunohistochemical analysis showed that compared with the stage
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y decreased ( Figure 7 ). The results of the immunohistochemical experiments are consistent with the conclusi
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33215029", "kind": "science-record", "revision": 6, "content_hash": "sha256:4c01ed3cbae730567b7e0f78737526f9b0544eabf9a26acf5535f63f5c84f71d", "created_at": "2026-11-01T15:41:16Z", "updated_at": "2026-11-01T21:24:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Using Machine Learning Modeling to Explore New Immune-Related Prognostic Markers in Non-Small Cell Lung Cancer.", "doi": "10.3389/fonc.2020.550002", "pmid": "33215029", "authors": ["Jiasheng Xu", "Han Nie", "Jiarui He", "Xinlu Wang", "Kaili Liao", "Luxia Tu", "Zhenfang Xiong"], "journal": "Frontiers in oncology", "year": 2020, "abstract": "OBJECTIVE: To find new immune-related prognostic markers for non-small cell lung cancer (NSCLC).\nMETHODS: We found GSE14814 is related to NSCLC in GEO database. The non-small cell lung cancer observation (NSCLC-OBS) group was evaluated for immunity and divided into high and low groups for differential gene screening according to the score of immune evaluation. A single factor COX regression analysis was performed to select the genes related to prognosis. A prognostic model was constructed by machine learning, and test whether the model has a test efficacy for prognosis. A chip-in-chip non-small cell lung cancer chemotherapy (NSCLC-ACT) sample was used as a validation dataset for the same validation and prognostic analysis of the model. The coexpression genes of hub genes were obtained by pearson analysis and gene enrichment, function enrichment and protein interaction analysis. The tumor samples of patients with different clinical stages were detected by immunohistochemistry and the expression difference of prognostic genes in tumor tissues of patients with different stages was compared.\nRESULTS: By screening, we found that LYN, C3, COPG2IT1, HLA.DQA1, and TNFRSF17 is closely related to prognosis. After machine learning, we constructed the immune prognosis model from these 5 genes, and the model AUC values were greater than 0.9 at three time periods of 1, 3, and 5 years; the total survival period of the low-risk group was significantly better than that of the high-risk group. The results of prognosis analysis in ACT samples were consistent with OBS groups. The coexpression genes are mainly involved B cell receptor signaling pathway and are mainly enriched in apoptotic cell clearance. Prognostic key genes are highly correlated with PDCD1, PDCD1LG2, LAG3, and CTLA4 immune checkpoints. The immunohistochemical results showed that the expression of COPG2IT1 and HLA.DQA1 in stage III increased significantly and the expression of LYN, C3, and TNFRSF17 in stage III decreased significantly compared with that of stage I. The experimental results are consistent with the previous analysis.\nCONCLUSION: LYN, C3, COPG2IT1, LA.DQA1, and NFRSF17 may be new immune markers to judge the prognosis of patients with non-small cell lung cancer.", "claims": [{"id": "claim-method", "statement": "Survival analysis was performed using Kaplan-Meier method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33215029", "locator": "sections[9] \"Statistical Analysis\" paragraph 2", "quote": "Survival analysis was performed using Kaplan-Meier method."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: the Gene Expression Omnibus (GSE14814).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33215029", "locator": "sections[19] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: the Gene Expression Omnibus (GSE14814)."}], "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:33215029"], "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:GSE14814"], "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:GSE14814"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33215029", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2020.550002", "sha256": "sha256:20cf85ff0cb1138b9b3733797088d3f28bd06c3cf4209f406d1e2b8a68ee2c6a", "bytes": 45113, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2020.550002", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7665579", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE14814", "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=GSE14814", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14814", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: the Gene Expression Omnibus (GSE14814).", "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: the Gene Expression Omnibus (GSE14814).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1267450", "GSM1267451", "GSM1267452", "GSM1267453", "GSM1267454", "GSM1267455", "GSM1267456", "GSM1267457", "GSM1267458", "GSM1267459", "GSM1267460", "GSM1267461", "GSM1267462", "GSM1267463", "GSM1267464", "GSM1267465", "GSM1267466", "GSM1267467", "GSM1267468", "GSM1267469", "GSM1267470", "GSM1267471", "GSM1267472", "GSM1267473", "GSM1267474", "GSM1267475", "GSM1267476", "GSM1267477", "GSM1267478", "GSM1267479", "GSM1267480", "GSM1267481", "GSM1267482", "GSM1267483", "GSM1267484", "GSM1267485", "GSM1267486", "GSM1267487", "GSM1267488", "GSM1267489", "GSM1267490", "GSM1267491", "GSM1267492", "GSM370913", "GSM370914", "GSM370915", "GSM370916", "GSM370917", "GSM370918", "GSM370919", "GSM370920", "GSM370921", "GSM370922", "GSM370923", "GSM370924", "GSM370925", "GSM370926", "GSM370927", "GSM370928", "GSM370929", "GSM370930", "GSM370931", 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"platform": "96", "taxon": "Homo sapiens", "title": "Prognostic and Predictive Gene Signature for Adjuvant Chemotherapy in Resected Non-Small-Cell Lung Cancer", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33215029:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:239ce5ddd71f329299e12e8cccbbb2245622d305c79d6110158d4d23921aa4b8", "bytes": 618, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#T1", "version": null, "note": "Basic information of patients in the stage I lung cancer group and stage III lung cancer group.", "structure": {"pmcid": "PMC7665579", "section_index": 8, "section_title": "Experimental Verification of Prognostic Genes", "row_count": 5, "column_count": 8}, "table": {"label": "Table 1", "caption": "Basic information of patients in the stage I lung cancer group and stage III lung cancer group.", "rows": [["Group", "Gender", "Age", "Cancer type", "Stage", "TNM", "Radiotherapy or chemotherapy"], ["Male", "Female"], ["Stage I lung cancer group", "26", "24", "52.8. ± 1.7", "22 cases of LUSC and 28 cases of LUAD", "I", "T1N0M0", "None"], ["Stage III lung cancer group", "27", "23", "54.6 ± 3.2", "24 cases of LUSC and 26 cases of LUAD", "IIIA", "T1N2M0", "None"], ["P value", ">0.05", ">0.05", ">0.05", "/"]], "row_count": 5, "column_count": 8, "numeric_cells": 11, "header_rows": 2, "locator": "section[8]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33215029:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6fc36780e95dcdbb5ba95f9a634a659fbf42ee810c6b8607c2cfb3443aa3925e", "bytes": 569, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#T2", "version": null, "note": "Expression of five prognostic related genes in the stage I lung cancer group and stage III lung cancer group.", "structure": {"pmcid": "PMC7665579", "section_index": 16, "section_title": "Experimental Verification of Prognostic Related Genes", "row_count": 6, "column_count": 4}, "table": {"label": "Table 2", "caption": "Expression of five prognostic related genes in the stage I lung cancer group and stage III lung cancer group.", "rows": [["Gene", "Stage I lung cancer group", "Stage III lung cancer group", "P value"], ["LYN", "9.3 ± 0.62", "2.5 ± 0.36", "<0.01"], ["C3", "8.9 ± 0.37", "2.1 ± 0.35", "<0.01"], ["COPG2IT1", "3.6 ± 0.59", "7.3 ± 0.26", "<0.05"], ["HLA.DQA1", "4.3 ± 0.87", "10.5 ± 1.12", "<0.05"], ["TNFRSF17", "7.8 ± 0.86", "3.2 ± 0.36", "<0.05"]], "row_count": 6, "column_count": 4, "numeric_cells": 16, "header_rows": 1, "locator": "section[16]/table-wrap[1]#T2"}}], "gaps": 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE14814"], "resolved_accessions": ["GSE14814"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: the Gene Expression Omnibus (GSE14814)."], "basis": "The paper names GSE14814 in Gene Expression Omnibus (GEO) 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:33215029", "data:geo:GSE14814", "asset:table:pmid:33215029:1", "asset:table:pmid:33215029:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE14814"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:24:19Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 35993, "completion_tokens": 984, "cached_tokens": 784}}, "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:33215029", "type": "paper", "label": "pmid:33215029"}, {"id": "source:pmid:33215029", "type": "manuscript", "label": "PMID 33215029 full text"}, {"id": "data:geo:GSE14814", "type": "dataset", "label": "GEO GSE14814"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33215029", "type": "paper", "label": "pmid:33215029"}, {"id": "source:pmid:33215029", "type": "manuscript", "label": "PMID 33215029 full text"}, {"id": "data:geo:GSE14814", "type": "dataset", "label": "GEO GSE14814"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33215029", "type": "extraction", "used": ["source:pmid:33215029"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE14814", "type": "accession_resolution", "used": ["data:geo:GSE14814"], "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:33215029", "parent_hash": "sha256:b5fd8e84147f4ef051a77c193299f2501f46a974499f062eeec26a8af4b2aa4e", "fork_of": null, "generation": 5}, "gaps": ["asset:data:geo:GSE14814 licence not read", "asset:data:geo:GSE14814 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["h different clinical stages were detected by immunohistochemistry and the expression difference of prognostic", "LG2, LAG3, and CTLA4 immune checkpoints. The immunohistochemical results showed that the expression of COPG2I", "tients are shown in Table 2 . The results of immunohistochemical analysis showed that compared with the stage", "y decreased ( Figure 7 ). The results of the immunohistochemical experiments are consistent with the conclusi"], "order_basis": "paper_text_order:1036", "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": ["Survival analysis was performed using Kaplan-Meier method."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}