ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2024; 15(12):3633-3644. doi:10.7150/jca.96100 This issue Cite
Research Paper
Spatial and Single-Cell Investigations Illuminate Theragnostic value and Immune Landscape of Mitochondrial Dynamin-Like GTPase in Breast Cancer
1. Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan.
2. Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
3. Department of Pathology, Show Chwan Memorial Hospital, Changhua 500, Taiwan.
4. Department of Allergy and Immunology, China Medical University Children's Hospital, Taichung 404, Taiwan.
5. Research Center for Allergy, Immunology, and Microbiome, China Medical University Hospital, Taichung 404, Taiwan.
6. Institute of Molecular & Cellular Biology, National Tsing Hua University, Hsinchu 300, Taiwan.
7. Comprehensive Breast Health Center, Taipei Veterans General Hospital, Taipei 112, Taiwan.
8. Division of Breast Surgery, Department of Surgery, Center for Cancer Research, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung 807, Taiwan.
9. Institute of Clinical Medicine, National Cheng Kung University, Tainan 704, Taiwan.
10. Department of Surgery, Kaohsiung Municipal Minsheng Hospital, Kaohsiung 802, Taiwan.
11. Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
12. Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan.
Abstract
Background: As we delve into the intricate world of mitochondrial inner membrane proteins, particularly Optic Atrophy types 1 and 3 (OPA1/3), we uncover their pivotal role in maintaining mitochondrial dynamic equilibrium and fusion, crucial for cellular energy production and synthesis. Despite extensive scrutiny, the significance of OPA1/3 in breast cancer (BRCA) and its interplay with the immune microenvironment remain elusive.
Materials and Methods: We meticulously sourced BRCA data from renowned repositories such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA), leveraging cutting-edge techniques including single-cell RNA-sequencing (scRNA-seq), spatial transcriptomics, and pharmacogenomics. Through multifaceted data analysis, we endeavored to unravel the intricate role and potential value of OPA1/3 in BRCA tumorigenesis and progression.
Results: Our investigation reveals a conspicuous upregulation of OPA1/3 expression in BRCA, correlating with dismal prognoses. Kaplan-Meier plot analysis underscores that heightened OPA1/3 levels are associated with poor survival rates. Both clinical specimens and biobank biopsies corroborate the elevated expression of OPA1/3 in breast cancer patients. Moreover, scRNA-seq unveils a strong correlation between OPA1/3 and macrophage infiltration in the BRCA immune milieu, alongside its association with the cellular communication network involving CXCL, TGFb, VEGF, and IL16.
Conclusion: In light of these findings, OPA1/3 emerges as a promising contender for therapeutic targeting and as a potential diagnostic, prognostic, and survival biomarker in BRCA. The implications of our study underscore the pressing need to explore these novel biomarkers to enhance patient outcomes.
Keywords: Breast cancer, Spatial transcriptomic, OPA, immune cell, Diagnostic biomarker
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