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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 Five Cytotoxicity-Related Genes Involved in the Progression of Triple-Negative Breast Cancer
Yan Zhang1,2,3, Gui-Hui Tong4, Xu-Xuan Wei2
1Department of Pathology, School of Basic Medical Sciences, Southern Medical University/Nanfang Hospital, Southern Medical University, Guangzhou, China.
Abstract:
Background: Breast cancer is one of the deadly tumors in women, and its incidence continues to increase. This study aimed to identify novel therapeutic molecules using RNA sequencing (RNA-seq) data of breast cancer from our hospital. Methods: 30 pairs of human breast cancer tissue and matched normal tissue were collected and RNA sequenced in our hospital. Differentially expressed genes (DEGs) were calculated with raw data by the R package "edgeR", and functionally annotated using R package "clusterProfiler". Tumor-infiltrating immune cells (TIICs) were estimated using a website tool TIMER 2.0. Effects of key genes on therapeutic efficacy were analyzed using RNA-seq data and drug sensitivity data from two databases: the Cancer Cell Line Encyclopedia (CCLE) and the Cancer Therapeutics Response Portal (CTRP). Results: There were 2,953 DEGs between cancerous and matched normal tissue, as well as 975 DEGs between primary breast cancer and metastatic breast cancer. These genes were primarily enriched in PI3K-Akt signaling pathway, calcium signaling pathway, cAMP signaling pathway, and cell cycle. Notably, CD8+ T cell, M0 macrophage, M1 macrophage, regulatory T cell and follicular helper T cell were significantly elevated in cancerous tissue as compared with matched normal tissue. Eventually, we found five genes (GALNTL5, MLIP, HMCN2, LRRN4CL, and DUOX2) were markedly corelated with CD8+ T cell infiltration and cytotoxicity, and associated with therapeutic response. Conclusion: We found five key genes associated with tumor progression, CD8+ T cell and therapeutic efficacy. The findings would provide potential molecular targets for the treatment of breast cancer.
Insights
This study identified five key genes (GALNTL5, MLIP, HMCN2, LRRN4CL, DUOX2) that correlate with CD8+ T cell infiltration and therapeutic response in breast cancer, offering potential new targets for treatment.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Breast cancer incidence is rising globally, necessitating novel therapeutic strategies.
- RNA sequencing (RNA-seq) is a powerful tool for identifying molecular targets in cancer.
- Understanding the tumor microenvironment, including immune cell infiltration, is crucial for effective cancer treatment.
Purpose of the Study:
- To identify novel therapeutic molecules for breast cancer using hospital-based RNA-seq data.
- To investigate the relationship between gene expression, immune cell infiltration, and therapeutic efficacy.
- To discover potential molecular targets for breast cancer treatment.
Main Methods:
- RNA sequencing of 30 pairs of breast cancer and matched normal tissues.
- Differential gene expression analysis using "edgeR" and functional annotation with "clusterProfiler".
- Estimation of tumor-infiltrating immune cells (TIICs) via TIMER 2.0 and analysis of gene effects on therapeutic efficacy using CCLE and CTRP databases.
Main Results:
- 2,953 differentially expressed genes (DEGs) identified between cancerous and normal tissues; 975 DEGs between primary and metastatic breast cancer.
- DEGs enriched in PI3K-Akt, calcium, cAMP signaling pathways, and cell cycle.
- Significant elevation of CD8+ T cells, M0/M1 macrophages, regulatory T cells, and follicular helper T cells in cancerous tissues. Five genes (GALNTL5, MLIP, HMCN2, LRRN4CL, DUOX2) strongly correlated with CD8+ T cell infiltration, cytotoxicity, and therapeutic response.
Conclusions:
- Five key genes identified are associated with breast cancer progression, CD8+ T cell infiltration, and therapeutic efficacy.
- These genes represent potential molecular targets for novel breast cancer therapies.
- Further research into these genes could lead to improved treatment strategies for breast cancer patients.
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