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pmid:39193519
Study of LY9 as a potential biomarker for prognosis and prediction of immunotherapy efficacy in lung adenocarcinoma.
Kun Deng · Liqiang Yuan · Zhanyu Xu · Fanglu Qin · Zhiwen Zheng · Liuliu Huang · Wei Jiang · Junqi Qin · Yu Sun · Tiaozhan Zheng · Xinhuai Ou · Liping Zheng · Shikang Li
PeerJ · 2024 doi:10.7717/peerj.17816
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Experiment
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Data
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Analysis
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Complete file
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Additionally, we conducted a correlation analysis of LY9 expression in LUAD with immune cell infiltration using the TIMER database and the CIBERSORT algorithm, and with immune checkpoints using the GEPIA database. Also, we constructed a potential ceRNA network for LY9. Furthermore, we explored LY9-related pathways by Gene Set Enrichment Analysis (GSEA). Finally, validation of differential expression at the mRNA level was obtained from the GEO database. We collected LUAD tissues for Quantitative Real-time PCR (qRT-PCR) to verify the expression of LY9, CD8, and CD4 and calculated the correlation between them. We also conducted immunohistochemistry (IHC) to verify the protein expression of LY9.\nResults: Results showed that LY9 was highly expressed in various tumors, including LUAD. Besides, patients with high LY9 expression presented longer overall survival (OS) and more multiple lymphocyte infiltrations. The expression of LY9 in LUAD strongly and positively correlates with multiple immune cell infiltration and immune checkpoints. The functional enrichment analysis indicated that LY9 was involved in multiple immune-related pathways and non-small cell lung cancer. Moreover, a ceRNA regulatory network of LINC00943-hsa-miR-141-3p-LY9 might be involved. Finally, GSE68465 dataset confirmed differential expression of LY9 mRNA levels in LUAD and the qRT-PCR results verified LY9 had a strong and positive correlation with CD4 and CD8 T cells. Unfortunately, IHC did not detect the expression of LY9 protein level in tumor tissues and WB experiments validated the protein expression of LY9 in the OCI-AML-2 cell line.\nConclusions: Therefore, we hypothesized that LY9 could serve as a potential, novel prognostic biomarker for LUAD and could predict immunotherapy efficacy at the mRNA level.", "claims": [{"id": "claim-method", "statement": "Then we conducted Cox analysis through Xenashiny website (https://shiny.zhoulab.ac.cn/UCSCXenaShiny/) to measure the prognostic value (overall survival, OS) of LY9 in 33 cancers from the TCGA database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39193519", "locator": "sections[3] \"Differential expression and prognostic value analysis of LY9 in pan-cancer\" paragraph 2", "quote": "Then we conducted Cox analysis through Xenashiny website (https://shiny.zhoulab.ac.cn/UCSCXenaShiny/) to measure the prognostic value (overall survival, OS) of LY9 in 33 cancers from the TCGA database."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data and worksheets are available in the Supplemental Files.The data from third parties are available at:(1). UCSC Xena database: GDC TCGA (gene expression RNAseq, HTSeq - FPKM);(2). Kaplan-Meier plotter: LY9 and select cancer type;(3). Gene Expression Profiling Interactive Analysis (GEPIA): LY9 and select cancer type; LY9,CD274, PDCD1, and CTLA4, LUAD(4). TargetScan 7.2 database: LY9;(5). DIANA-tools database LncBase Experimental v.2: hsa-miR-141-3p(6). TIMER 2.0 database: LY9,CD274, PDCD1, and CTLA4, LUAD", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39193519", "locator": "sections[21] \"Additional Information and Declarations\" paragraph 5", "quote": "The raw data and worksheets are available in the Supplemental Files.The data from third parties are available at:(1). UCSC Xena database: GDC TCGA (gene expression RNAseq, HTSeq - FPKM);(2). Kaplan-Meier plotter: LY9 and select cancer type;(3). Gene Expression Profiling Interactive Analysis (GEPIA): LY9 and select cancer type; LY9,CD274, PDCD1, and CTLA4, LUAD(4). TargetScan 7.2 database: LY9;(5). DIANA-tools database LncBase Experimental v.2: hsa-miR-141-3p(6). TIMER 2.0 database: LY9,CD274, PDCD1, and CTLA4, LUAD"}], "state": "complete"}, {"id": "claim-target-result", "statement": "Patients with high LY9 expression presented longer overall survival (OS) and more multiple lymphocyte infiltrations.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39193519", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Besides, patients with high LY9 expression presented longer overall survival (OS) and more multiple lymphocyte infiltrations."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Patients with high LY9 expression presented longer overall survival (OS) and more multiple lymphocyte infiltrations.", "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:39193519"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39193519", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.17816", "sha256": "sha256:c61d387d9d899e14fb6398bce96d464d1fc53bec50b9b16bc482b52b64f97418", "bytes": 42451, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.17816", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11348898", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "Then we conducted Cox analysis through Xenashiny website (https://shiny.zhoulab.ac.cn/UCSCXenaShiny/) to measure the prognostic value (overall survival, OS) of LY9 in 33 cancers from the TCGA database."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "KM"}}, {"id": "method-4", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.8, "band": "high", "quote": "limma"}}], "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["logrank_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: log_rank_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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We collected LUAD tissues for Quantitative Real-time PCR (qRT-PCR) to verify the expression of LY9, C"], "order_basis": "paper_text_order:837", "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": ["correlation between them. We also conducted immunohistochemistry (IHC) to verify the protein expression of LY", "hem. We also conducted immunohistochemistry (IHC) to verify the protein expression of LY9. Re", "ion with CD4 and CD8 T cells. Unfortunately, IHC did not detect the expression of LY9 protein"], "order_basis": "paper_text_order:971", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["logrank_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Then we conducted Cox analysis through Xenashiny website (https://shiny.zhoulab.ac.cn/UCSCXenaShiny/) to measure the prognostic value (overall survival, OS) of LY9 in 33 cancers from the TCGA database."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}