Abstract

Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of cancer death in the world. It is a disease that encompasses a variety of molecular alterations, including in non-coding RNAs such as circular RNAs (circRNAs). In the present study, we investigated hsa_circ_0000211, hsa_circ_0000284, hsa_circ_0000524, hsa_circ_0001136 and hsa_circ_0004771 expression profiles using RT-qPCR in 71 gastric tissue samples from GC patients (tumor and tumor-adjacent samples) and volunteers without cancer. In order to investigate the suitability of circRNAs as minimally invasive biomarkers, we also evaluated their expression profile through RT-qPCR in peripheral blood samples from patients with and without GC (n = 41). We also investigated the predicted interactions between circRNA-miRNA-mRNA and circRNA-RBP using the KEGG and Reactome databases. Overall, our results showed that hsa_circ_0000211, hsa_circ_0000284 and hsa_circ_0004771 presented equivalent expression profiles when analyzed by different methods (RNA-Seq and RT-qPCR) and different types of samples (tissue and blood). Further, functional enrichment results identified important signaling pathways related to GC. Thus, our data support the consideration of circRNAs as new, minimally invasive biomarkers capable of aiding in the diagnosis of GC and with great potential to be applied in clinical practice.

Highlights

  • Gastric cancer (GC) is the fifth most common type of cancer in the world, but diagnosis is usually made in late and advanced stages

  • Five circRNAs were upregulated in GC and adjacent tissue (ADJ) when compared to non-cancer tissue (NC) [18]

  • Such circRNAs are important because they were already described as miRNA sponges [26,27,28,29] and as we explored their possible roles in GC, we found that they are involved in several pathways relevant to cancer development, such as apoptosis pathway and p53 signaling pathway

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Summary

Introduction

Gastric cancer (GC) is the fifth most common type of cancer in the world, but diagnosis is usually made in late and advanced stages This is the main reason for poor prognosis among gastric cancer patients, leading it to be the third most common cause of cancer deaths, at one in every thirteen cancer deaths in the world [1,2]. As it is a biologically heterogeneous disease, GC patients harbor several genetic and epigenetic alterations [3,4], among which we highlight the differential expression of regulatory non-coding RNAs (ncRNAs). While providing a better understanding of the regulatory mechanisms carried out by these molecules, the investigation of such epigenetic elements may lead to the discovery of new biomarkers that are sufficiently sensitive and specific, improving aspects related to late diagnosis and response to treatment [7].

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