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.

Frontiers in Genetics
|January 20, 2022
PubMed

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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