Related Experiment Video
Updated: Dec 6, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Screening and Identification of Key Biomarkers in Acquired Lapatinib-Resistant Breast Cancer
Shengnan Bao1,2, Yi Chen1,2, Fan Yang1,2
1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
Lapatinib, targeting the human epidermal growth factor receptor family members HER1 and HER2, has been approved by the US Food and Drug Administration for use in metastatic HER2-positive breast cancer. However, resistance to lapatinib remains a common challenge to HER2-positive metastatic breast cancer. Until now, the molecular mechanisms of acquired resistance to lapatinib (ALR) have remained unclear. With no definite biomarkers currently known, we aimed to screen for key biomarkers in ALR. In this research, we identified 55 differentially expressed genes (DEGs, 20 upregulated, 35 downregulated) through bioinformatic analysis using microarray datasets GSE16179, GSE38376, and GSE51889 from the Gene Expression Omnibus (GEO) database. The related gene function was explored using the Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed with the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. The functional enrichment of the DEGs was analyzed, including negative regulation of the B cell apoptotic process, DNA replication, solute:proton symporter activity, synthesis, and degradation of ketone bodies, and metal sequestration by antimicrobial proteins. Analysis of seven hub genes revealed their concentration mainly in DNA replication and cell cycle. Survival analysis revealed that MCM10 and SPC24 may be related with poor prognosis in patients with ALR. Meanwhile, the prediction model of lapatinib sensitivity was constructed, and emerging role of the model was further analyzed using several webtools. In conclusion, hub genes are involved in the complex mechanisms underlying ALR in breast cancer and provide favorable support for treatment of ALR in future.
Insights
Acquired resistance to lapatinib (ALR) in HER2-positive breast cancer is a challenge. This study identified key genes, including MCM10 and SPC24, involved in ALR mechanisms and prognosis, aiding future treatment strategies.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Lapatinib is approved for HER2-positive metastatic breast cancer but acquired resistance (ALR) is a significant clinical challenge.
- The molecular mechanisms underlying ALR and predictive biomarkers remain largely undefined.
- Understanding ALR is crucial for improving treatment outcomes in patients with HER2-positive breast cancer.
Purpose of the Study:
- To identify key biomarkers associated with acquired lapatinib resistance (ALR) in HER2-positive breast cancer.
- To elucidate the molecular mechanisms and pathways involved in ALR.
- To develop a predictive model for lapatinib sensitivity.
Main Methods:
- Bioinformatic analysis of microarray datasets (GSE16179, GSE38376, GSE51889) from the Gene Expression Omnibus (GEO) database.
- Identification of differentially expressed genes (DEGs) and construction of protein-protein interaction (PPI) networks using STRING and Cytoscape.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, including survival analysis and prediction model construction.
Main Results:
- Identified 55 differentially expressed genes (DEGs) in ALR, with 20 upregulated and 35 downregulated.
- Functional enrichment analysis highlighted pathways such as DNA replication, cell cycle, and B cell apoptotic process.
- Seven hub genes were identified, with MCM10 and SPC24 associated with poor prognosis in ALR patients.
Conclusions:
- Hub genes, particularly MCM10 and SPC24, play a role in the complex mechanisms of ALR in breast cancer.
- These findings provide potential biomarkers for predicting lapatinib sensitivity and prognosis.
- The identified genes and pathways offer support for developing novel therapeutic strategies for ALR.
