Identification of a Gene Expression Signature to Predict the Risk of Early Recurrence and the Degree of Immune Cell Infiltration in Triple-negative Breast Cancer

• Published in: Cancer genomics & proteomics Vol. 21; no. 3; pp. 316 - 326
• Main Authors: Sato, Keiko, Miura, Kentaro, Tamori, Shoma, Akimoto, Kazunori
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.05.2024
• Subjects: Biomarkers; Biomarkers, Tumor - genetics; Breast cancer; CD6 antigen; Cell death; Clinical trials; Datasets; DNA microarrays; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Humans; Immune status; Immune system; Immunotherapy; Infiltration; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Metastases; Middle Aged; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - immunology; Neoplasm Recurrence, Local - pathology; Patients; Prognosis; Risk; Stat4 protein; Therapeutic targets; Transcriptome; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - immunology; Triple Negative Breast Neoplasms - pathology; Tumor microenvironment; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; Tumors; recurrence; immune cell infiltration; gene expression signature; TNBC; biomarker
• ISSN: 1109-6535; 1790-6245
• DOI: 10.21873/cgp.20450

Patients with triple-negative breast cancer (TNBC) have a high rate of recurrence within 3 years of diagnosis and a high rate of death within 5 years compared to other subtypes. The number of clinical trials investigating various new agents and combination therapies has recently increased; however, current strategies benefit only a minority of patients. This study aimed to identify specific genes that predict patients at high risk of recurrence and the immune status of the tumor microenvironment at an early stage, thereby providing insight into potential therapeutic targets to improve clinical outcomes in TNBC patients. We evaluated the prognostic significance of microarray mRNA expression of 20,603 genes in 233 TNBC patients from the METABRIC dataset and further validated the results using RNA-seq mRNA expression data in 143 TNBC patients from the GSE96058 dataset. Eighteen differentially expressed genes (AKNA, ARHGAP30, CA9, CD3D, CD3G, CD6, CXCR6, CYSLTR1, DOCK10, ENO1, FLT3LG, IFNG, IL2RB, LPXN, PRKCB, PVRIG, RASSF5, and STAT4) identified in both datasets were found to be reliable biomarkers for predicting TNBC recurrence and progression. Notably, the genes whose low expression was associated with increased risk of recurrence and death were immune-related genes, with significant differences in levels of immune cell infiltration in the tumor microenvironment between high- and low- expression groups. Genes reported herein may be effective biomarkers to identify TNBC patients who will and will not benefit from immunotherapy and may be particularly important genes for developing future treatment strategies, including immunotherapy.