Circulating microRNA‐1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma

Abstract

Aims Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. Methods We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real‐time quantitative reverse transcription–polymerase chain reaction (PCR). Results Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA‐1246 (miR‐1246). Quantitative PCR confirmed that miR‐1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR‐1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR‐1246 was associated with aggressive tumor characteristics, including tumor–node–metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR‐1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528–5.071; P = 0.0008). Conclusion Circulating miR‐1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.

Usefulness of serum miR‑1246/miR‑106b ratio in patients with esophageal squamous cell carcinoma

“…miR-1246 was shown to have elevated serum levels in patients with ESCC in our previous study. Since then, other researchers have reported increased serum levels of this miR in other carcinomas ( 31 , 32 ). In a systematic review of gastrointestinal cancer, it was reported that the expression of miR-1246 in serum is more useful as a biomarker than that of miR-21, which is an oncomiR ( 12 ).…”

Selection and validation of miR-1280 as a suitable endogenous normalizer for qRT-PCR Analysis of serum microRNA expression in Hepatocellular Carcinoma

“…In order to determine the effect of different combinations of reference genes in the normalization of a miRNA of interest, the RT-qPCR expression profile of three miRNAs related to HCC 34,35 , miR-1246, miR4454 and miR4443, was assessed at all time points. The differential expression of the three miRNAs resulted statistically significant only when normalized with miR-1280 compared to U6, which ranked second after the overall stability evaluation.…”

“…In order to determine the effect of different normalizers on the expression of circulating miRNAs, we profiled miR-1246, miR-4454 and miR-4443 during the follow-up of the patients. The three miRNAs were selected according to their possible relevance in HCC 34,35 . We compared the performances of the two highest-ranked normalizers, miR-1280 and U6.…”

Reversal of doxorubicin resistance in lung cancer cells by neferine is explained by nuclear factor erythroid-derived 2-like 2 mediated lung resistance protein down regulation

“…Several studies identified circulating miRNAs as therapy predictive markers [98] . Chuma et al [99] reported that serum miR-1246 predicted early tumor recurrence after hepatic resection. Cho et al [100] revealed that the levels of circulating miR-26a and miR-29a before treatment were prognostic markers for liver transplantation-free survival in hepatitis B virus-related HCC patients.…”