Dados do Resumo

Título

Tumor-educated platelets as a source of potential biomarkers in colorectal cancer: an in silico investigation

Introdução

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, with current diagnostic methods relying on invasive procedures and serum markers of low sensitivity. Recent studies suggest that platelets can be educated by tumors, altering their molecular signature to create tumor-educated platelets (TEPs). Due to their abundance in blood, TEPs could serve as a minimally invasive source of diagnostic and predictive biomarkers for several cancer types, including CRC.

Objetivo

To identify genes differentially expressed in TEPs from CRC patients, which may serve as potential diagnostic biomarkers.

Métodos

A total of 144 high-throughput RNA sequencing samples were analyzed, comprising platelets isolated from 72 CRC patients and 72 healthy controls obtained from two public databases available on the Gene Expression Omnibus (GEO), under the identification number GSE183635 and GSE68086. The low-quality reads were removed using FastP and the high-quality reads were aligned to the human genome using the GRCh38.p13 v42 reference index with Salmon. In RStudio, the reads were imported from Salmon using the Tximport package. Differential gene expression analysis was performed with the DESeq2 package. Genes with a |log2FoldChange| value > 1 and an adjusted p-value < 0.01 were considered upregulated. The Receiver Operating Characteristic (ROC) curve was calculated using the pROC package, in which values > 0.8 were applied to the upregulated genes. The Gene Ontology (GO) Enrichment Analysis was conducted utilizing the clusterProfiler package, with an adjusted p-value < 0.05 considered significant.

Resultados

We identified 3,087 differentially expressed genes (DEGs), of which 1,658 (8.4%) were upregulated in TEPs from CRC patients and 1,429 (7.2%) were downregulated in healthy controls. The top 15 upregulated genes were selected based on the criteria established previously, these genes are: TLN1, DGKZ, SSBP3, IGF2BP2, MINK1, MAP1A, MYL9, PARVB, GPSM3, CAMTA2, SF3A2, NUCB1, BRD4, FKBP8, and DMTN. Their respective area under the curve (AUC) values were 0.86, 0.86, 0.85, 0.84, 0.84, 0.84, 0.84, 0.84, 0.83, 0.83, 0.83, 0.83, 0,82, 0,82 and 0.82. Functional enrichment analysis of these genes showed significant enrichment for processes related to platelet activation, blood coagulation, platelet aggregation, cell-substrate adhesion, regulation of cell-matrix adhesion, actin binding, and transcriptional coactivator activity.

Conclusões

We identified 15 genes differentially expressed in TEPs of CRC patients. These genes are involved in critical processes related to tumor progression and could serve as potential biomarkers for the detection of this disease.

Financiador do resumo

315643/2023-4

Palavras Chave

tumor educated platelets; precision medicine; biomarkers