Serum lncRNAs, NBAT-1, and FOXCUT signature in hepatocellular carcinoma developed on top of chronic hepatitis C

Background: Hepatocellular Carcinoma (HCC) is a universal health problem responsible for 8.2% of all cancer deaths. Numerous risk factors were documented to be contributed to HCC development with viral hepatitis C ranking as the major predisposing factor in Egypt. The presence of a detectable amount of long noncoding RNAs (lncRNAs) in the circulation is linked to the development and spread of tumors. LncRNAs NBAT-1 and FOXCUT expression levels were used as genetic markers for the detection of gastrointestinal tract cancers. We hypothesized that serum expression levels of NBAT-1 and FOXCUT are new biomarkers for HCC that are related to laboratory and pathological markers.

Patients and methods: This study included 165 hepatitis C virus (HCV)-related HCC Egyptian patients, 180 HCV-infected noncancer patients, and 180 healthy controls, the serum expression levels of NBAT-1 and FOXCUT were measured by using quantitative real-time polymerase chain reaction.

Results: This study's results include that medians (inter-quartile range [IQRs]) of NBAT-1 in HCC and HCV patients were (1.9 [0.87-4.94], 10.01 [7.34-13.29] respectively) which exhibited significantly higher expression than controls, while the medians (IQRs) of FOXCUT in HCC and HCV patients were (0.15 [0.04-0.52], 6.42 [2.49-10.10], respectively) that exhibited significantly lower expression than controls regarding HCC patients but significantly higher expression than controls regarding HCV patients. In comparing serum fold changes of NBAT-1 and FOXCUT between HCC patients and HCV patients; we obtained significantly higher levels of target genes in HCV patients (p < 0.001) than in HCC patients. Also, a positive correlation was detected between NBAT-1 and FOXCUT in HCC group (r = 0.262, p = 0.001) and in HCV group (r = 0.937, p < 0.001). Higher serum NBAT-1 and FOXCUT were significantly associated with better clinical and laboratory data of the disease. Multivariate regression analysis showed that FOXCUT was an independent predictor for HCC among HCV patients (p < 0.001).

Conclusion: Our study cited that NBAT-1 and FOXCUT could be considered new diagnostic serum biomarkers for HCC on top of HCV.