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Expression of metabolism-related proteins in triple-negative breast cancer
Min-Ju Kim1, Do-Hee Kim1, Woo-Hee Jung1
1Department of Pathology, Severance Hospital, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine Seoul, South Korea.
Abstract:
To investigate the dominant metabolic type of triple-negative breast cancer (TNBC) and evaluate its clinical implication through analysis of protein expression related to glycolysis, glutaminolysis, and mitochondrial oxidative phosphorylation. Tissue samples from 129 patients with TNBC who underwent mastectomy due to invasive breast cancer from 2000 to 2005 were prepared for tissue microarray. By immunohistochemical staining of the tissue microarrays, the markers of glycolysis-related proteins (Glut-1, CAIX, MCT4), glutaminolysis-related proteins (GLS1, GDH, ASCT2), and mitochondrial enzymes (ATP synthase, SDHA and SDHB) were analyzed. Based on the results, the metabolic phenotypes were defined based on positivity for more than two of three markers for each phenotype as follows: glycolysis type (Glut-1, CAIX and MCT4), glutaminolysis type (GLS1, GDH and ASCT2) and mitochondrial type (ATP synthase, SDHA and SDHB). The percentages of samples with metabolic phenotypes of tumor and stroma of TNBC were as follows: for tumor, mitochondrial type (85.3%)>glutaminolysis type (67.4%)>glycolysis type (63.0%); and for stroma, glutaminolysis type (37.2%)>glycolysis type (16.3%)>mitochondrial type (14.0%). The most common metabolic phenotype of TNBC was glycolysis type for basal-like type and non-glycolysis type for non-basal-like type (p=0.047). The correlation between glutaminolysis and mitochondrial type was statistically significant in both tumor and stroma (p<0.001). In conclusion, tumor cells of TNBC express glycolysis and mitochondrial metabolism-related proteins. Glycolysis type is the most common phenotype of basal-like type, and reversely, non-glycolysis type is the most common phenotype of non basal-like type.
Insights
Triple-negative breast cancer (TNBC) predominantly exhibits mitochondrial and glycolysis-related protein expression. The basal-like subtype shows a glycolysis metabolic phenotype, while non-basal-like subtypes display a non-glycolysis phenotype.
Area of Science:
- Oncology
- Cancer Metabolism
- Biochemistry
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies.
- Understanding TNBC's metabolic landscape is crucial for developing novel treatment strategies.
- Metabolic reprogramming, including glycolysis, glutaminolysis, and oxidative phosphorylation, is a hallmark of cancer.
Purpose of the Study:
- To identify the dominant metabolic phenotype in TNBC.
- To analyze protein expression related to glycolysis, glutaminolysis, and mitochondrial oxidative phosphorylation.
- To evaluate the clinical implications of these metabolic phenotypes in TNBC.
Main Methods:
- Tissue microarrays from 129 TNBC patients were analyzed using immunohistochemical staining.
- Protein markers for glycolysis (Glut-1, CAIX, MCT4), glutaminolysis (GLS1, GDH, ASCT2), and mitochondrial enzymes (ATP synthase, SDHA, SDHB) were assessed.
- Metabolic phenotypes were defined based on the expression of these markers.
Main Results:
- In TNBC tumors, the mitochondrial type (85.3%) was most prevalent, followed by glutaminolysis (67.4%) and glycolysis (63.0%).
- In TNBC stroma, glutaminolysis (37.2%) was most common, followed by glycolysis (16.3%) and mitochondrial (14.0%).
- A significant correlation was observed between glutaminolysis and mitochondrial types in both tumor and stroma (p<0.001).
- The basal-like subtype predominantly showed a glycolysis phenotype, while non-basal-like subtypes exhibited a non-glycolysis phenotype (p=0.047).
Conclusions:
- TNBC tumor cells express proteins associated with both glycolysis and mitochondrial metabolism.
- The metabolic phenotype of TNBC is linked to its molecular subtype, with basal-like tumors favoring glycolysis.
- These findings highlight distinct metabolic profiles within TNBC, offering potential therapeutic targets.
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