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.

Highlights

  • Breast cancer is a deadliest type of female carcinoma (Xu et al, 2021), the incidence of breast cancer is increasing in the past few years (Hu et al, 2021; Su et al, 2021; Tagliamento et al, 2021; Xu et al, 2021)

  • A total of 30 patients with diagnosed triple-negative breast cancer were included in this study, including 15 breast cancer with lymph node metastasis and 15 breast cancer without lymph node metastasis from our hospital. 30 pairs of cancerous tissue and matched normal tissue were obtained from these 30 breast cancer patients

  • To identify key genes throughout the oncogenesis and progression of breast cancer, we first performed differential expression analysis using RNA sequencing (RNA-seq) data of 30 pairs of breast tissues from 30 Triple-negative breast cancer (TNBC) patients enrolled in this study, and performed differential expression analysis using RNA-seq data from 15 TNBC with lymph node metastasis and 15 TNBC without lymph node metastasis

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Summary

Introduction

Breast cancer is a deadliest type of female carcinoma (Xu et al, 2021), the incidence of breast cancer is increasing in the past few years (Hu et al, 2021; Su et al, 2021; Tagliamento et al, 2021; Xu et al, 2021). The mortality and recurrence rate of TNBC is higher than other types of breast cancer; especially in the first 5 years after diagnosis, the mortality and recurrence rate are significantly higher than other types of breast cancer (Dent et al, 2007). Primary or secondary resistance to the treatment restrained the present therapeutic strategy. Facing this grim situation, it is very urgent to identify new molecular targets to treat resistant TNBC. This study aimed to identify novel therapeutic molecules using RNA sequencing (RNA-seq) data of breast cancer from our hospital

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