RESUMO
Recent trends are moving towards the use of the circulating transcriptome as a potential diagnostic and therapeutic tool for hepatocellular carcinoma (HCC). The aim of this study is to identify circulatory RNA based biomarker panel, in addition to their relationship to the outcome in HCC. First, utilizing bioinformatics tools, we selected an HCC-specific RNA-based biomarker panel that depended on the integration of suppressor of glucose autophagy-associated (SOGA1) gene expression with the chosen panel of epigenetic regulators of this gene [long non-coding RNA antisense for X-inactive-specific transcript (lncRNA-TSIX) and microRNA-548-a-3p (miR-548-a-3p)]. Second, we attempted to validate these biomarkers using the sera of 65 patients with HCC, 34 patients with chronic hepatitis C virus (CHC) infection and 32 healthy volunteers. Finally, the expression levels of the chosen RNA-based biomarker panel were assessed in the serum samples using qRT-PCR assays. The panel of 3 RNA-based biomarkers (lncRNA-TSIX, miR-548-a-3p, and SOGA1) exhibited high sensitivity and specificity in differentiating HCC patients from CHC patients and healthy controls. Among these 3 RNAs, serum lncRNA-TSIX and SOGA1 were independent prognostic factor. The chosen circulatory RNA-based biomarker panel may serve as a diagnostic and prognostic biomarker for HCC.
Assuntos
Carcinoma Hepatocelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Feminino , Hepatite C Crônica/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Sensibilidade e EspecificidadeRESUMO
The original publication has been updated. The family name of Alaa Habieb contained a typo that has now been corrected.
RESUMO
The competing endogenous RNA networks play a pivotal role in cancer diagnosis and progression. Novel properstrategies for early detection of colorectal cancer (CRC) are strongly needed. We investigated a novel CRC-specific RNA-based integrated competing endogenous network composed of lethal3 malignant brain tumor like1 (L3MBTL1) gene, long non-coding intergenic RNA- (lncRNA RP11-909B2.1) and homo sapiens microRNA-595 (hsa-miRNA-595) using in silico data analysis. RT-qPCR-based validation of the network was achieved in serum of 70 patients with CRC, 40 patients with benign colorectal neoplasm, and 20 healthy controls. Moreover, in cancer tissues of 20 of the 70 CRC cases were involved in the study. The expression of RNA-based biomarker network in both CRC and adjacent non-tumor tissues and their correlation with the serum levels of this network members was investigated. Lastly, the expression levels of the chosen ceRNA was verified in CRC cell line. Our results revealed that the three RNAs-based biomarker network (long non-coding intergenic RNA-[lncRNA RP11-909B2.1], Homo sapiens microRNA-595 [hsa-miRNA-595], and L3MBTL1 mRNA), had high sensitivity and specificity for discriminating CRC from healthy controls and also from benign colorectal neoplasm. The data suggest that among these three RNAs, serum lncRNA RP11-909B2.1 could be a promising independent prognostic factors in CRC. The circulatory RNA based biomarker panel can act as potential biomarker for CRC diagnosis and prognosis.