Dados do Resumo

Título

Differential Analysis of Gene Expression in Tumor-Educated Platelets from Metastatic Breast Cancer Patients

Introdução

Breast cancer (BC) corresponds to the most malignant disease and the major cancer-related death in women worldwide. Approximately 20-30% of BC cases progress to metastasis, significantly reducing patient survival. Tumors can educate platelets, leading to the formation of tumor-educated platelets (TEPs), which play a critical role in cancer progression, particularly in metastasis. Recently, TEPs have emerged as minimally invasive sources of biomarkers for various solid tumors, including BC.

Objetivo

Identify differentially expressed genes in TEPs from metastatic BC patients that could be potential metastasis biomarkers.

Métodos

RNA-seq data from BC patients were downloaded from the Gene Expression Omnibus (GEO) under the accession number GSE183635. Low-quality reads were filtered out using FastP, and the remaining high-quality reads were aligned to the human genome (GRCh38.p13 v43) using the Salmon tool. The aligned reads were imported into RStudio via the Tximport package for further analysis. Differential gene expression analysis was conducted with the DESeq2 package, considering genes with |log2FoldChange| > 0.5 and an adjusted p-value < 0.05 as upregulated. The Receiver Operating Characteristic (ROC) curve was generated using the pROC package, with a threshold value of > 0.75 applied. Gene Ontology (GO) enrichment analysis was performed using the clusterProfiler package.

Resultados

We found 75 differentially expressed genes (DEGs), of which 57 (0.39%) were upregulated, and 18 (0.12%) were downregulated in TEPs from metastatic BC patients compared to nonmetastatic. TYMP, CASP4, ACYP2, TMEM258, ENSG00000288796, SMIM27, UBXN11, and HPSE were selected based on previous criteria with AUC values of 0.79, 0.78, 0.77, 0.76, 0.75, 0.75 and 0.75, respectively. GO enrichment analysis of upregulated genes revealed their participation in lysosomal membrane, lytic vacuole membrane, and vacuolar membrane composition and participation of coenzyme A metabolic process.

Conclusões

We identified eight genes differentially expressed in TEPs from metastatic BC patients, suggesting their potential as biomarkers for metastasis.

Financiador do resumo

409332/2021-6

Palavras Chave

tumor-educated platelets; Metastasis; Liquid Biopsy