Evaluation of a lipid peroxidation-dependent ferroptosis RNA panel expression as a potential noninvasive biomarker in patients with nonalcoholic steatohepatitis-associated hepatocellular carcinoma.

BACKGROUND

Nonalcoholic steatohepatitis (NASH) is a major cause of hepatocellular carcinoma (HCC) and is the fastest growing etiology of HCC worldwide. A sensitive non-invasive marker for the diagnosis, screening, or clinical monitoring of NASH-HCC, however, has yet to be established.

METHODS AND

RESULTS

We used reverse transcription quantitative real-time PCR (RT-qPCR) to evaluate the expression of a bioinformatically-retrieved RNA panel related to lipid peroxidation-dependent ferroptosis in 193 subjects. The area under the receiver operating characteristic (ROC) curve was calculated to assess its diagnostic performance in discriminating NASH-associated HCC in NASH cases. ROC analysis indicated that the selected ferroptosis-related RNAs had various diagnostic performances. GPX4 had great potential in distinguishing NASH-associated HCC from NASH (AUC (SE) = 0.999 (0.002), P < 0.0001), which was superior to alpha-fetoprotein (AFP) and the recently developed GALAD score. Additionally, for the first time, we proposed that miR-762 has a critical role in NASH-associated HCC which can add to the unique molecular pattern of this etiology.

CONCLUSIONS

Our study indicates that this RNA panel has significant superiority with respect to the current biomarkers for NASH-HCC diagnosis, and it is promising for clinical application and as a therapeutic target after further validation.