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ITM2A as a potential prognostic marker for triple-negative breast cancer
Can Jiang1, Ruixin Feng1, Yongqian Zhao1
1Department of Pathology, Xiangya Hospital, Xiangya School of Basic Medical Sciences, Central South University, Changsha, China.
Abstract:
Different subtypes of breast cancer pose great challenges for precision therapy, especially triple-negative breast cancer (TNBC), because it lacks effective therapeutic targets and is highly resistant to chemotherapy. In this study, the transmembrane protein ITM2A was systematically identified as a novel prognostic biomarker and potential therapeutic target for TNBC. ITM2A was found to be significantly under expressed in TNBC tissues, as revealed by differential expression profiling. Furthermore, patients exhibiting low ITM2A expression demonstrated worse overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). A combined multi-omics analysis revealed a significant association between low ITM2A expression and immunosuppressive microenvironmental features. It is noteworthy that the ITM2A high-expression group exhibited substantial clinical benefits in anti-PD-L1 treatment (AUC=0.982) and CAR-T treatment (AUC=0.827). Gene Ontology functional annotation and KEGG pathway enrichment analysis indicated that ITM2A may coordinate anti-tumor immune responses by regulating copper ion metabolic reprogramming and immune checkpoint networks. Pharmacogenomic analysis further confirmed that the expression level of ITM2A was negatively correlated with the sensitivity of etoposide. By establishing the 'immunometabolism-therapeutic response' regulatory axis of ITM2A, this study hopes to provide an innovative theoretical basis for the targeted treatment of TNBC and the precise stratification of immunotherapy.
Insights
The transmembrane protein ITM2A is a novel biomarker for triple-negative breast cancer (TNBC). Low ITM2A expression correlates with poor survival and predicts response to immunotherapy, offering new therapeutic strategies.
Area of Science:
- Oncology
- Immunology
- Biomarker Discovery
Background:
- Triple-negative breast cancer (TNBC) presents significant challenges for targeted therapy due to a lack of effective targets and chemoresistance.
- Identifying novel prognostic biomarkers and therapeutic targets is crucial for improving TNBC patient outcomes.
Purpose of the Study:
- To identify the transmembrane protein ITM2A as a novel prognostic biomarker and potential therapeutic target for TNBC.
- To investigate the association between ITM2A expression and the tumor microenvironment, treatment response, and patient survival.
Main Methods:
- Differential gene expression profiling and multi-omics analysis were used to identify and validate ITM2A.
- Gene Ontology and KEGG pathway analyses were performed to understand ITM2A's functional role.
- Pharmacogenomic analysis assessed the correlation between ITM2A expression and drug sensitivity.
Main Results:
- ITM2A was significantly underexpressed in TNBC tissues, with low expression linked to worse overall survival, recurrence-free survival, and distant metastasis-free survival.
- Low ITM2A expression was associated with an immunosuppressive tumor microenvironment.
- High ITM2A expression predicted significant clinical benefits from anti-PD-L1 and CAR-T immunotherapies.
- ITM2A regulates anti-tumor immunity via copper ion metabolism and immune checkpoints, and its expression is inversely correlated with etoposide sensitivity.
Conclusions:
- ITM2A serves as a novel prognostic biomarker and potential therapeutic target for TNBC.
- The study establishes an 'immunometabolism-therapeutic response' axis for ITM2A, providing a basis for targeted TNBC treatment and immunotherapy stratification.
