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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
Identification of ribosomal protein family in triple-negative breast cancer by bioinformatics analysis
Ziyue Lin1, Rui Peng2, Yan Sun1
1Department of Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Abstract:
Triple-negative breast cancer (TNBC) accounts for ∼20% of all breast cancer (BC) cases. The management of TNBC represents a challenge due to its worse prognosis, heterogeneity and lack of targeted therapy. Moreover, its mechanisms are not fully clear. The aim of the study is to identify crucial genes between TNBC and non-TNBC for underlying targets for diagnostic and therapeutic methods of TNBC. The differentially expressed genes (DEGs) between TNBC and non-TNBC were selected from the Gene Expression Omnibus (GEO) database after the integrated analysis of two datasets (GSE65194 and GSE76124). Then Gene ontology (GO) and KEGG analysis were performed by DAVID database, protein-protein interaction (PPI) of DEGs was constructed by Search Tool for the Retrieval of Reciprocity Genes (STRING) database. Furthermore, centrality analysis and module analysis were carried out by Cytoscape to analyze the TNBC-related PPI. Subsequently, overall survival (OS) analysis was performed by GEPIA. Finally, the expressions of these key genes in TNBC and non-TNBC tissues were tested by qRT-PCR. The results showed that 955 DEGs were obtained, which were mainly enriched in ribosome, ribosomal subunit, and so on. Moreover, 19 candidate genes were focused on by centrality analysis and module analysis. Furthermore, we found the low expressions of ribosomal protein S9 (RPS9), ribosomal protein S14 (RPS14), ribosomal protein S27 (RPS27), ribosomal protein L11 (RPL11) and ribosomal protein L14 (RPL14) were related to a poor OS in BC patients. Additionally, qRT-PCR results suggested that these five genes were notably down-regulated in TNBC tissues. In summary, the present study suggests that ribosomal proteins are related to TNBC, and they may play an important role in the diagnosis, treatment and prognosis of TNBC.
Insights
Triple-negative breast cancer (TNBC) is challenging to treat. This study identifies five ribosomal protein genes (RPS9, RPS14, RPS27, RPL11, RPL14) that are down-regulated in TNBC and linked to poor survival, offering potential diagnostic and therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) constitutes 20% of breast cancer cases.
- TNBC presents significant management challenges due to its poor prognosis, heterogeneity, and lack of targeted therapies.
- The underlying molecular mechanisms of TNBC remain incompletely understood.
Purpose of the Study:
- To identify key genes differentiating TNBC from non-TNBC.
- To uncover potential diagnostic and therapeutic targets for TNBC.
- To elucidate the role of specific genes in TNBC progression and patient survival.
Main Methods:
- Integrated analysis of two Gene Expression Omnibus (GEO) datasets (GSE65194, GSE76124) to identify differentially expressed genes (DEGs).
- Gene Ontology (GO) and KEGG pathway analysis using DAVID; Protein-Protein Interaction (PPI) network construction using STRING.
- Network analysis (Cytoscape) for centrality and module identification, followed by overall survival (OS) analysis using GEPIA and qRT-PCR validation.
Main Results:
- Identified 955 DEGs, primarily enriched in ribosomal and ribosomal subunit functions.
- Network analysis highlighted 19 candidate genes, with five ribosomal proteins (RPS9, RPS14, RPS27, RPL11, RPL14) showing significant associations.
- Low expression of these five ribosomal proteins correlated with poor OS in breast cancer patients and were notably down-regulated in TNBC tissues.
Conclusions:
- Ribosomal proteins are implicated in TNBC pathogenesis.
- The identified ribosomal proteins (RPS9, RPS14, RPS27, RPL11, RPL14) represent potential biomarkers for TNBC diagnosis.
- These genes may serve as novel therapeutic targets for improving TNBC treatment and prognosis.
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