Dados do Resumo

Título

Differential Profiling of miRNAs in Tumor-Educated Platelets Associated with Colorectal Cancer

Introdução

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Emerging evidence indicates that tumors can reprogram blood platelets into tumor-educated platelets (TEPs), which support tumor progression. TEPs present a promising source for the development of cancer biomarkers. Among the components of TEPs, microRNAs (miRNAs)—small RNA molecules comprising 20–22 nucleotides—play a critical role in modulating tumor gene expression.

Objetivo

We aimed to identify differentially expressed miRNAs that could be potential diagnostic biomarkers of colorectal cancer patients.

Métodos

Data expressions were obtained from the Gene Expression Omnibus (GEO) with accession numbers GSE183635 and GSE68086. The dataset included 144 high-throughput RNA sequencing samples comprising platelets isolated from 72 colorectal cancer (CRC) patients and 72 healthy controls. Low-quality reads were removed using FastP, and high-quality reads were aligned to the human genome (GRCh38.p13 v42 reference index) using Salmon. In RStudio, reads from Salmon were imported using the Tximport package, and only miRNAs were filtered for further analysis. Differential gene expression analysis was performed with the DESeq2 package, considering genes with |log2FoldChange| > 1 and an adjusted p-value < 0.05 as upregulated. The Receiver Operating Characteristic (ROC) curve was generated using the pROC package, with values > 0.75 deemed relevant. Gene Ontology (GO) Enrichment Analysis was conducted using the clusterProfiler package.

Resultados

We found 214 differentially expressed miRNA, of which 98 (5.4%) were upregulated while 116 (6.4%) were downregulated in TEPs from CRC patients compared to healthy controls. The upregulated transcripts that met the criteria previously established were AK1, AP1B1, ATP2A3, ATN1, ANK1, and ARL2. Their respective area under the curve (AUC) values were 0.81, 0.81, 0.79, 0.78, 0.78 and 0.77. Functional enrichment analysis of these genes revealed significant enrichment in processes related to hemoglobin metabolism, maintenance of cell polarity, regulation of aerobic respiration, and regulation of cellular respiration.

Conclusões

We identified six miRNAs that were upregulated in TEPs from CRC patients, which are potentially linked to tumor development.

Palavras Chave

tumor-educated platelets; miRNA; Diagnosis