Research Paper Volume 16, Issue 1 pp 322—347
Clinical significance and immune characteristics analysis of miR-221-3p and its key target genes related to epithelial-mesenchymal transition in breast cancer
- 1 The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- 2 Department of Central Laboratory, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- 3 Department of Breast, Jiangmen Central Hospital, Jiangmen 529000, Guangdong, China
Received: July 20, 2023 Accepted: November 20, 2023 Published: January 6, 2024
https://doi.org/10.18632/aging.205370How to Cite
Copyright: © 2024 Fang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: MicroRNA-221-3p (miR-221-3p) facilitates the advancement of breast cancer (BC) through the induction of epithelial-mesenchymal transition (EMT). Our research aimed to utilize bioinformatics to discover possible EMT-related target genes (ETGs) of miR-221-3p and examine their roles in breast cancer.
Methods: We employed bioinformatics techniques to identify ten key ETGs of miR-221-3p. Subsequently, we conducted an extensive analysis of both miR-221-3p and the ten ETGs, including clinical significance and immune characteristics.
Results: The expression of miR-221-3p was notably higher in Basal-like BC compared to other subtypes and adjacent normal tissue. Our pathway analysis suggested that miR-221-3p might regulate EMT through the MAPK signaling pathway by targeting its ETGs. Among the ETGs, seven core genes (EGFR, IGF1, KDR, FGF2, KIT, FGFR1, and FGF1) exhibited downregulation in BC. Conversely, ERBB2, SDC1, and MMP14 showed upregulation in BC and displayed potential diagnostic value. The analysis of prognostication indicated that increased levels of SDC1 and MMP14 were correlated with an unfavorable prognosis, whereas elevated expression of KIT was associated with a more favorable prognosis. The infiltration of various immune cells and the expression of immune checkpoint genes (ICGs) exhibited positive correlations with most ETGs and miR-221-3p. SDC1 exhibited a greater tumor mutational burden (TMB) score, while ERBB2, KDR, FGF2, KIT, FGFR1, and FGF1 showed lower TMB scores. Furthermore, decreased ERBB2 and KDR expression levels were correlated with elevated microsatellite instability (MSI) scores. Elevated expression of ETGs was linked to decreased mRNA stemness indices (mRNAsi), whereas miR-221-3p displayed the opposite pattern. Most ETGs and miR-221-3p expression exhibited a negative correlation with IC50 values for drugs. Among the ETGs, amplification was the most significant genetic alteration, except for IGF1.
Conclusion: In conclusion, miR-221-3p acts as a unique indicator for Basal-like BC. The examination revealed ten essential ETGs of miR-221-3p, some of which show potential as diagnostic and prognostic markers. The in-depth examination of these ten ETGs and miR-221-3p indicates their participation in the development of BC, emphasizing their promise as innovative targets for therapy in BC patients.
Abbreviations
BC: breast cancer; EMT: epithelial-mesenchymal transition; miRNAs: MicroRNAs; miR-221-3p: microRNA-221-3p; TCGA: The Cancer Genome Atlas; RPM: read per million; GEO: Gene Expression Omnibus; DEGs: differentially expressed genes; ETGs: EMT-related target genes; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; PPI: protein-protein interaction; TPM: Transcripts Per Million; ROC: Receiver Operating Characteristic; qRT-PCR: quantitative real-time PCR; IHC: immunohistochemistry; KM: Kaplan-Meier; OS: overall survival; DSS: disease-specific survival; ICGs: immune checkpoint genes; TMB: tumor mutational burden; MSI: microsatellite instability; mRNAsi: mRNA expression-based stemness index; HER2: human epidermal growth factor receptor 2; ER: estrogen receptor; PR: progesterone receptor; AUC: area under the curve; EGFR: epidermal growth factor receptor; IGF1: insulin-like growth factor 1; ERBB2: Erb-b2 receptor tyrosine kinase 2; KDR: kinase insert domain receptor; FGF: fibroblast growth factor; KIT: KIT proto-oncogene receptor tyrosine kinase; FGFR: fibroblast growth factor receptor; SDC1: syndecan-1; MMP: matrix metalloproteinase.