Abstract
Regarded as the most invasive subtype, triple-negative breast cancer (TNBC) lacks the expression of estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2) proteins. Platelets have recently been shown to be associated with metastasis of malignant tumors. Nevertheless, the status of platelet-related genes in TNBC and their correlation with patient prognosis remain unknown. In this study, the expression and variation levels of platelet-related genes were identified and patients with TNBC were divided into three subtypes. We collected cohorts from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, we constructed a seven-gene signature which classified the two cohorts of patients with TNBC into low- or high-risk groups. Patients in the high-risk group were more likely to have lower survival rates than those in the low-risk group. The risk score, incorporated with the clinical features, was confirmed as an independent factor for predicting the overall survival (OS) time. Functional enrichment analyses revealed the involvement of a variety of vital biological processes and classical cancer-related pathways that could be important to the ultimate prognosis of TNBC. We then built a nomogram that performed well. Moreover, we tested the model in other cohorts and obtained positive outcomes. In conclusion, platelet-related genes were closely related to TNBC, and this novel signature could serve as a tool for the assessment of clinical prognosis.
Highlights
Breast cancer (BC) remains a primary disease burden for women worldwide (Britt et al, 2020)
The expression levels of 480 platelet-related genes were compared between samples from 115 patients with triple-negative breast cancer (TNBC) and 113 normal samples in the The Cancer Genome Atlas (TCGA)-BRCA cohort, and 177 differentially expressed genes (DEGs) were identified
We performed functional enrichment analyses including Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO), and the results showed that DEGs were directly related to the platelets (Figures 2C,D), including platelet activation, degranulation, and aggregation (Supplementary Table S3)
Summary
Breast cancer (BC) remains a primary disease burden for women worldwide (Britt et al, 2020). According to the expression of estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2) proteins, BC can be divided into several subtypes, and each lead to certain therapeutic sensitivities and prognoses (Heer et al, 2020). Among these subtypes, triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancer cases (Carey et al, 2010). Due to its chemoresistance and unfavorable prognosis, treatment of TNBC is still a major challenge and considered to be a “black hole” compared to other BC subtypes (Zheng et al, 2020a). Given the limitations of TNBC treatments, there is an urgent need to explore novel targets to
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