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pmid:39669152

Dynamic changes in serum adenosine and the adenosine metabolism-based signature for prognosis in HER2-positive metastatic breast cancer patients.

Lijun Wang · Yizhi Ge · Li Yin · Dan Zong · Yang Li · Jianfeng Wu · Xia He

Heliyon · 2024 doi:10.1016/j.heliyon.2024.e39545

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Experiment

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Data

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title
Dynamic changes in serum adenosine and the adenosine metabolism-based signature for prognosis in HER2-positive metastatic breast cancer patients.
doi
10.1016/j.heliyon.2024.e39545
pmid
39669152
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[0]
Lijun Wang
[1]
Yizhi Ge
[2]
Li Yin
[3]
Dan Zong
[4]
Yang Li
[5]
Jianfeng Wu
[6]
Xia He
journal
Heliyon
year
2024
abstract
Aims: Adenosine metabolism in the breast cancer microenvironment is critical for tumor immunity. However, the prognostic significance of adenosine in breast cancer remains unclear. We aimed to dynamically monitor serum adenosine levels in patients with HER2-positive metastatic breast cancer (MBC) patients and to explore its predictive significance in trastuzumab therapy. Methods: The sequencing and clinical data were downloaded from TCGA and GSE176078. Adenosine-related differentially expressed genes was analyzed by "DESeq2" package. Multivariate Cox and lasso-penalized Cox regressions were used to construct prognostic risk signatures. The risk scores were calculated from the identified expression of the hub genes. Bioinformatic analyses were performed using R with related packages. We also enrolled the metastatic breast cancer patients with HER2-positive from in our center and classified them into different groups according to the clinical outcomes assessed by enhanced CT. The adenosine levels were dynamically detected, and the difference in immune microenvironment between the subgroups was assessed by the immune cells that were recorded in our center. Results: A total of 109 breast cancer patients with HER2-positive MBC were enrolled, and the expressions of 22 adenosine-related genes were filtered and matched from the TCGA database. The survival model based on the 15 differentially expressed genes was established, and the risk scores of each patient were the prognostic risk factors. Single-cell transcriptome sequencing data identified transcriptomic differences in patients with HER2-positive breast cancer. We also confirmed the predictive value of serum adenosine in the clinical progression of HER2-positive MBC patients. The different immune microenvironment between the subgroups supported the reliability of the predictive ability of adenosine in HER2-positive MBC patients. Conclusions: The dynamic change of adenosine is a predictive biomarker for monitoring disease progression. The adenosine metabolism-based signature has the potential application in the prognosis of HER2-positive MBC patients.
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To assess the association between adenosine-related risk scores and overall survival (OS), we constructed a multivariate Cox proportional hazards regression model. Additionally, we used the lasso-penalized Cox regression method for variable selection and to prevent overfitting.
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To assess the association between adenosine-related risk scores and overall survival (OS), we constructed a multivariate Cox proportional hazards regression model. Additionally, we used the lasso-penalized Cox regression method for variable selection and to prevent overfitting.
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The information of TCGA and GSE176078 can be found at the following website: https://portal.gdc.cancer.gov/, https://www.ncbi.nlm.nih.gov/. The data that support the findings of this study are available in this article and its supplementary files. Further inquiries can be directed to the corresponding authors.
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The information of TCGA and GSE176078 can be found at the following website: https://portal.gdc.cancer.gov/, https://www.ncbi.nlm.nih.gov/. The data that support the findings of this study are available in this article and its supplementary files. Further inquiries can be directed to the corresponding authors.
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Patients with high adenosine-based risk scores had shorter OS than those with low-risk scores (HR, 17; 95 % CI, 5–56, P < 0.001, Fig. 1F).
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Patients with high adenosine-based risk scores had shorter OS than those with low-risk scores (HR, 17; 95 % CI, 5–56, P < 0.001, Fig. 1F).
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sections[18] "Mutation landscape and adenosine-related survival analyses" paragraph 3
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Patients with high adenosine-based risk scores had shorter OS than those with low-risk scores (HR, 17; 95 % CI, 5–56, P < 0.001, Fig. 1F).
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Patients with high adenosine-based risk scores had shorter OS than those with low-risk scores (HR, 17; 95 % CI, 5–56, P < 0.001, Fig. 1F).
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ing. The immune cell counts were analyzed by flow cytometry. Briefly, single-cell suspension was prepare
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in HER2-positive breast cancer patients. All patients were assigned to the high- or low-risk groups based on the
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activity. Benefiting from the advantages of scRNA-seq technology, we revealed the high-resolution
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We aimed to dynamically monitor serum adenosine levels in patients with HER2-positive metastatic breast cancer (MBC) patients and to explore its predictive significance in trastuzumab therapy.\nMethods: The sequencing and clinical data were downloaded from TCGA and GSE176078. Adenosine-related differentially expressed genes was analyzed by \"DESeq2\" package. Multivariate Cox and lasso-penalized Cox regressions were used to construct prognostic risk signatures. The risk scores were calculated from the identified expression of the hub genes. Bioinformatic analyses were performed using R with related packages. We also enrolled the metastatic breast cancer patients with HER2-positive from in our center and classified them into different groups according to the clinical outcomes assessed by enhanced CT. The adenosine levels were dynamically detected, and the difference in immune microenvironment between the subgroups was assessed by the immune cells that were recorded in our center.\nResults: A total of 109 breast cancer patients with HER2-positive MBC were enrolled, and the expressions of 22 adenosine-related genes were filtered and matched from the TCGA database. The survival model based on the 15 differentially expressed genes was established, and the risk scores of each patient were the prognostic risk factors. Single-cell transcriptome sequencing data identified transcriptomic differences in patients with HER2-positive breast cancer. We also confirmed the predictive value of serum adenosine in the clinical progression of HER2-positive MBC patients. The different immune microenvironment between the subgroups supported the reliability of the predictive ability of adenosine in HER2-positive MBC patients.\nConclusions: The dynamic change of adenosine is a predictive biomarker for monitoring disease progression. The adenosine metabolism-based signature has the potential application in the prognosis of HER2-positive MBC patients.", "claims": [{"id": "claim-method", "statement": "To assess the association between adenosine-related risk scores and overall survival (OS), we constructed a multivariate Cox proportional hazards regression model. Additionally, we used the lasso-penalized Cox regression method for variable selection and to prevent overfitting.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39669152", "locator": "sections[15] \"Statistical analysis\" paragraph 2", "quote": "To assess the association between adenosine-related risk scores and overall survival (OS), we constructed a multivariate Cox proportional hazards regression model. Additionally, we used the lasso-penalized Cox regression method for variable selection and to prevent overfitting."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The information of TCGA and GSE176078 can be found at the following website: https://portal.gdc.cancer.gov/, https://www.ncbi.nlm.nih.gov/. The data that support the findings of this study are available in this article and its supplementary files. Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39669152", "locator": "sections[26] \"Data availability statements\" paragraph 2", "quote": "The information of TCGA and GSE176078 can be found at the following website: https://portal.gdc.cancer.gov/, https://www.ncbi.nlm.nih.gov/. The data that support the findings of this study are available in this article and its supplementary files. Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Patients with high adenosine-based risk scores had shorter OS than those with low-risk scores (HR, 17; 95 % CI, 5–56, P < 0.001, Fig. 1F).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Patients with high adenosine-based risk scores had shorter OS than those with low-risk scores (HR, 17; 95 % CI, 5–56, P < 0.001, Fig. 1F)."}, "evidence": [{"asset": "source:pmid:39669152", "locator": "sections[18] \"Mutation landscape and adenosine-related survival analyses\" paragraph 3", "quote": "Patients with high adenosine-based risk scores had shorter OS than those with low-risk scores (HR, 17; 95 % CI, 5–56, P < 0.001, Fig. 1F)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Patients with high adenosine-based risk scores had shorter OS than those with low-risk scores (HR, 17; 95 % CI, 5–56, P < 0.001, Fig. 1F).", "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:39669152"], "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:GSE176078"], "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:GSE176078"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39669152", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2024.e39545", "sha256": "sha256:be76aebd3f3dc45ecfb65ff90f7e958a3873ece4a26c47900dbf703ed5838b9e", "bytes": 44178, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.heliyon.2024.e39545", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11636132", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE176078", "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=GSE176078", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE176078", "version": null, "note": "The information of TCGA and GSE176078 can be found at the following website: https://portal.gdc.cancer.gov/, https://www.ncbi.nlm.nih.gov/. 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The immune cell counts were analyzed by flow cytometry. Briefly, single-cell suspension was prepare", "odies were added in an appropriate volume of flow cytometry staining solution and the cells. Gently puls", "more than 30 min. The cells were washed with flow cytometry staining solution and centrifuged at room te", "he staining solution and analyze the samples flow cytometry. Natural killer (NK) cells were marked by CD"], "order_basis": "paper_text_order:7195", "id": "assay:1"}, {"role": "data_generation", "definition_id": "clinical_trial", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["in HER2-positive breast cancer patients. All patients were assigned to the high- or low-risk groups based on the"], "order_basis": "paper_text_order:11932", "id": "assay:2"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["activity. Benefiting from the advantages of scRNA-seq technology, we revealed the high-resolution"], "order_basis": "paper_text_order:14871", "id": "assay:3"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ntly suggested the hyperactive histiocytosis in vivo. CfDNA levels can be used to evaluate the cu"], "order_basis": "paper_text_order:17885", "id": "assay:4"}, {"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": ["To assess the association between adenosine-related risk scores and overall survival (OS), we constructed a multivariate Cox proportional hazards regression model. Additionally, we used the lasso-penalized Cox regression method for variable selection and to prevent overfitting."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}