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Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
Prognostic value of comprehensive typing based on m6A and gene cluster in TNBC
Haoming Wu1,2, Jikun Feng2, Jundong Wu1
1The Breast Center, Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Background:
Triple-negative breast cancer (TNBC) is resistant to targeted therapy with HER2 monoclonal antibodies and endocrine therapy, because it lacks the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC is a subtype of breast cancer with the worst prognosis and the highest mortality rate compared to other subtypes. N6-methyladenosine (m6A) modification is significant in cancer and metastasis, because it can alter gene expression and function at numerous levels, such as RNA splicing, stability, translocation, and translation. There are limited investigations into the connection between TNBC and m6A.
Materials And Methods:
Breast cancer-related data were retrieved from the Cancer Genome Atlas (TCGA) database, and 116 triple-negative breast cancer cases were identified from the data. The GSE31519 data set, which included 68 cases of TNBC, was obtained from the Gene Expression Omnibus (GEO) database. Survival analysis was used to determine the prognosis of distinct m6A types based on their m6A group, gene group, and m6A score. To investigate the potential mechanism, GO and KEGG analyses were performed on the differentially expressed genes.
Results:
The expression of m6A-related genes and their impact on prognosis in TNBC patients were studied. According to the findings, m6A was crucial in determining the prognosis of TNBC patients, and the major m6A-linked genes in this process were YTHDF2, RBM15B, IGFBP3, and WTAP. YTHDF2, RBM15B and IGFBP3 are associated with poor prognosis, while WTAP is associated with good prognosis. By cluster analysis, the gene cluster and the m6A cluster were beneficial in predicting the prognosis of TNBC patients. The m6A score based on m6A and gene clusters was more effective in predicting the prognosis of TNBC patients. Furthermore, the tumor microenvironment may play an important role in the process of m6A, influencing TNBC prognosis.
Conclusions:
N6-adenylic acid methylation (m6A) was important in altering the prognosis of TNBC patients, and the key m6A-associated genes in this process were YTHDF2, RBM15B, IGFBP3, and WTAP. Furthermore, the comprehensive typing based on m6A and gene clusters was useful in predicting TNBC patients' prognosis, showing potential as valuable evaluating tools for TNBC.
Insights
N6-methyladenosine (m6A) modification is crucial for triple-negative breast cancer (TNBC) prognosis. Key genes like YTHDF2 and WTAP, along with m6A scores, help predict patient outcomes, offering new diagnostic tools.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Triple-negative breast cancer (TNBC) lacks ER, PR, and HER2, leading to resistance against targeted therapies and poor prognosis.
- N6-methyladenosine (m6A) RNA modification influences gene expression and is implicated in cancer progression and metastasis.
- Limited research exists on the specific role of m6A in TNBC.
Purpose of the Study:
- To investigate the expression of m6A-related genes in TNBC.
- To determine the prognostic significance of m6A modification patterns in TNBC patients.
- To explore the potential mechanisms, including gene expression and tumor microenvironment interactions, influenced by m6A in TNBC.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases for TNBC patient data (116 and 68 cases, respectively).
- Performed survival analysis to correlate m6A patterns (m6A groups, gene groups, m6A score) with patient prognosis.
- Conducted Gene Ontology (GO) and KEGG pathway analyses to identify potential molecular mechanisms of differentially expressed genes.
Main Results:
- m6A modification plays a critical role in determining TNBC patient prognosis.
- Key m6A-associated genes impacting prognosis include YTHDF2, RBM15B, and IGFBP3 (poor prognosis) and WTAP (good prognosis).
- m6A and gene clustering, along with an integrated m6A score, effectively predicted TNBC prognosis, with the tumor microenvironment potentially influencing these outcomes.
Conclusions:
- m6A is a significant factor in TNBC prognosis, with specific genes (YTHDF2, RBM15B, IGFBP3, WTAP) being key players.
- Comprehensive typing based on m6A and gene clusters provides a valuable tool for predicting TNBC patient prognosis.
- These findings highlight m6A-based strategies as potential diagnostic and prognostic indicators for TNBC.
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