CELL INTELLIGENCE · 肿瘤细胞治疗研究

Triple‑negative breast cancer (TNBC) is a highly aggressive and heterogeneous subtype of breast cancer that lacks expression of estrogen receptor, progesterone receptor, and HER2, making it more challenging to treat with targeted therapies. The present study aimed to identify CD8+ T cell‑associated genes, which could provide insight into the mechanisms underlying TNBC to facilitate developing novel immunotherapies. TNBC datasets were downloaded from public databases including The Cancer Genome Atlas, Molecular Taxonomy of Breast Cancer International Consortium, and Gene Expression Omnibus. Candidate genes were identified integrating weighted gene co‑expression network analysis (WGCNA), differential gene expression, protein‑protein‑interaction network construction and univariate Cox regression analysis. Kaplan‑Meier survival, multivariate Cox regression and receiver operating characteristic analysis were performed to evaluate the prognostic value of hub genes. Knockdown experiments, alongside wound healing, Cell Counting Kit‑8 and Transwell migration and invasion assays were performed. In total, seven gene modules were associated with CD8+ T cells using WGCNA, among which potassium channel tetramerization domain 5 (KCTD5) was significantly upregulated in TNBC samples and was associated with poor prognosis. KCTD5 expression inversely associated with infiltration ratios of 'Macrophages M1', 'Plasma cells', and 'γδ T cells', but positively with 'activated Mast cells', 'Macrophages M0', and 'Macrophages M2'. As an independent prognostic indicator for TNBC, KCTD5 was also associated with drug sensitivity and the expression of programmed cell death protein 1, Cytotoxic T‑Lymphocyte‑Associated Protein 4 (CTLA4), CD274), Cluster of Differentiation 86 (CD86), Lymphocyte‑Activation Gene 3 (LAG3), T Cell Immunoreceptor with Ig and ITIM Domains (TIGIT). Knockdown of KCTD5 significantly inhibited viability, migration and invasion of TNBC cells in vitro . KCTD5 was suggested to impact the tumor immune microenvironment by influencing the infiltration of immune cells and may serve as a potential therapeutic target for TNBC.