Abstract
Objectives
This study aims to develop and validate a prognostic signature based on 7-methylguanosine-related (M7G-related) miRNAs for predicting prognosis and immune implications in breast invasive carcinoma (BRCA).
Materials and methods
M7G-related miRNA data of BRCA were obtained from The Cancer Genome Atlas (TCGA). Least absolute shrinkage and selection operator (LASSO)-penalized, univariate, and multivariate Cox regression analyses were used to construct the prognostic signature. Furthermore, the predictive validity was verified using Kaplan–Meier (KM) survival risk and receiver operating characteristic (ROC) plots. Internal random sampling verification was used to simplify and validate the signature. RT-qPCR was used to quantify the expression level of transcriptional profiles. The independent prognostic role of the risk score was validated using univariate and multivariate regression. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used for functional and immune enrichment analysis.
Results
A total of 18 M7G-related miRNAs were identified to construct the prognostic signature in BRCA. The low-risk group exhibited significantly higher overall survival than the high-risk group in the KM survival plot (P < 0.001). The area under the curve (AUC) for 1-, 3-, and 5-year survivals in the ROC curve were 0.737, 0.724, and 0.702, respectively. The survival significance in the training and testing cohorts was confirmed by random sampling verification. The most prominent miRNAs in the signature were the miR-7, miR-139, miR-10b, and miR-4728. Furthermore, immune scores for B, mast, and Th1 cells varied between risk groups. Our research demonstrated that CD52 was the most positively correlated gene with immune cells and functions in BRCA.
Conclusion
Our study presents a comprehensive and systematic analysis of M7G-related miRNAs to construct a prognostic signature in BRCA. The signature demonstrated excellent prognostic validity, with the risk score as an independent prognostic factor. These results provide critical evidence for further investigation of M7G miRNAs and offer new insights for BRCA patients in the context of effective immunotherapy.
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Data availability
TCGA: https://portal.gdc.cancer.gov/repository; TargetScan: https://www.targetscan.org/vert_80/; Gencode: https://www.gencodegenes.org/; miRbase: https://www.mirbase.org/; MDAnderson bioinformatics center: https://bioinformatics.mdanderson.org/estimate/disease.html; KEGG: https://www.genome.jp/kegg/; GO: http://geneontology.org/docs/go-enrichment-analysis/.
Abbreviations
- M7G:
-
7-Methylguanosine
- miRNA:
-
MicroRNA
- BRCA:
-
Breast invasive carcinoma
- TCGA:
-
The cancer genome atlas
- LASSO:
-
Least absolute shrinkage and selection operator
- KM:
-
Kaplan–Meier
- ROC:
-
Receiver operating characteristic
- ssGSEA:
-
Single sample gene set enrichment analysis
- AUC:
-
Area under curve
- BC:
-
Breast cancer
- METTL1:
-
Methyltransferase like 1
- WDR4:
-
WD repeat domain 4
- HCC:
-
Hepatocellular carcinoma
- CAFs:
-
Cancer associated fibroblasts
- TME:
-
Tumor microenvironment
- EMT:
-
Epithelial-mesenchymal transition
- MRBCmiRs:
-
M7G related breast invasive carcinoma miRNAs
- MRDEmiRs:
-
M7G related different expression miRNAs
- DERRmRs:
-
Different expressed risk-score related mRNAs
- DEIRmRs:
-
Different expressed immune-score related mRNAs
- PCA:
-
Principal component analysis
- KEGG:
-
Kyoto encyclopedia of genes and genomes
- DO:
-
Disease ontology
- GO:
-
Gene ontology
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Acknowledgements
We appreciate the databases of TCGA, Targetscan, Gencode, miRbase, MDAnderson bioinformatics center, KEGG and GO for the availability of the data.
Funding
This article was funded by the Fundamental Research Funds for the Central Universities of Central South University (Grant Nos.2021zzts0371). The funding doesn’t influence study design, collection, analysis and interpretation of data; the writing of the report; and the decision to submit the article for publication.
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AYL, TX and HL: Conceptualization, Formal analysis. AYL and HNX: Writing original draft. AYL, TX and HL: Review, Editing. AYL, ZYZ, CX, YX, BY, PXW, and ZYC: Visualization, Methodology. TX and HL: Supervision.
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Li, AY., Xiao, HN., Zhao, ZY. et al. Prognostic and immune implications of a novel 7-methylguanosine-related microRNA signature in breast invasive carcinoma: from exploration to validation. J Cancer Res Clin Oncol 149, 9105–9128 (2023). https://doi.org/10.1007/s00432-023-04849-1
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DOI: https://doi.org/10.1007/s00432-023-04849-1