A novel microRNAs expression signature for hepatocellular carcinoma diagnosis and prognosis

Abstract

This study aims to identify prognostic microRNAs (miRNAs) biomarkers for diagnosis and survival of hepatocellular carcinoma (HCC) based on large patients cohort analysis. HCC patient cohort data were downloaded from The Cancer Genome Atlas, including paired HCC and adjacent non-cancer tissues. Receiver operating characteristic curve method was used to classify cancer and non-cancer tissues according to microRNAs expression levels. The aberrant microRNAs expression level were ranked and risked for building a prognostic miRNAs signature model. Kaplan–Meier survival was used to analyze the differences among various risk factors in accordance with miRNAs ranking scores. The study showed 33-miRNA signature, 11 were down-regulated and 22 were up-regulated through comparison between cancer samples and non-cancer samples. The maximum correct classification rate is up to 98.7%. Five microRNAs, hsa-mir-3677, hsa-mir-421, hsa-mir-326, hsa-mir-424 and hsa-mir-511-2, significantly correlated with patient survival. The survival rate and time negatively associated with lowering miRNAs index. In the low risk group, over 70% patients showed 5 years survival, while none patients survived longer than 5 years in the high risk group. MiR-424, miR-326 and miR-511 could be applied for HCC diagnostic biomarkers. These five miRNAs were significantly associated with lysosome pathway and D-Glutamine and D-glutamate metabolism pathway via Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology annotation. Conclusively, the five miRNAs expression signature could be used as HCC prognostic and diagnostic biomarkers.

Targeting of TLE3 by miR‑3677 in human breast cancer promotes cell proliferation, migration and invasion

“…Another study by Wang et al (15) indicated that miR-217 promotes the proliferation and invasion of BC by repressing tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein-γ. miR-3677 correlates significantly with the survival time of patients with hepatocellular carcinoma (16)(17)(18). However, the biological function of miR-3677 in BC remains yet to be fully investigated.…”

MicroRNA-421 inhibits caspase-10 expression and promotes breast cancer progression

“…miR-421 has been regarded as an onco-microRNA in various types of cancers, including neuroblastoma [15,16], gastric cancer [8], lung adenocarcinoma [7], pancreatic cancer [9], hepatocellular carcinoma [5,9], and nasopharyngeal carcinoma [17], etc. It is reported that miR-421 was also upregulated in IBC compared to non-IBC [4].…”

“…Compared with those in corresponding non-tumor tissue, miRNA-421 was found to be highly expressed in tissue from hepatocellular carcinoma [5], osteosarcoma [6], lung adenocarcinoma [7], gastric cancer [8], and pancreatic cancer [9]. Furthermore, in patients with hepatocellular carcinoma [5], osteosarcoma [6], or gastric cancer [8], high expression levels of miR-421 were associated with poor prognosis. However, the clinical significance of miR-421 in patients with breast cancer is still to be investigated.…”

Systems Challenges of Hepatic Carcinomas: A Review

“…In addition, miRNAs regulate their target gene expression, involved in biological processes such as apoptosis, cell cycle regulation, angiogenesis, and metastasis and the miRNAs targeted genes mainly acts as enzyme binding, dehydrogenase, and glutamate transmembrane transporter and so on. 68,69 HCC includes several secondary conditions cirrhosis, viral infection, fibrosis, and inflammation, and miRNA biomarkers being not specific, could have been triggered by any of the above mentioned conditions, which is a caveat in the assessment of using miRNAs in HCC. As multiple miR-NAs target genes, it would be reasonable to select a panel of deregulated miRNAs that can be used as a diagnostic tool in HCC.…”