Novel biomarker genes for the prediction of post-hepatectomy survival of patients with NAFLD-related hepatocellular carcinoma.

BACKGROUND: The incidence and prevalence of nonalcoholic fatty liver disease related hepatocellular carcinoma (NAFLD-HCC) are rapidly increasing worldwide. This study aimed to identify biomarker genes for prognostic prediction model of NAFLD-HCC hepatectomy by integrating text-mining, clinical follow-up information, transcriptomic data and experimental validation. METHODS: The tumor and adjacent normal liver samples collected from 13 NAFLD-HCC and 12 HBV-HCC patients were sequenced using RNA-Seq. A novel text-mining strategy, explainable gene ontology fingerprint approach, was utilized to screen NAFLD-HCC featured gene sets and cell types, and the results were validated through a series of lab experiments. A risk score calculated by the multivariate Cox regression model using discovered key genes was established and evaluated based on 47 patients' follow-up information. RESULTS: Differentially expressed genes associated with NAFLD-HCC specific tumor microenvironment were screened, of which FABP4 and VWF were featured by previous reports. A risk prediction model consisting of FABP4, VWF, gender and TNM stage were then established based on 47 samples. The model showed that overall survival in the high-risk score group was lower compared with that in the low-risk score group (p = 0.0095). CONCLUSIONS: This study provided the landscape of NAFLD-HCC transcriptome, and elucidated that our model could predict hepatectomy prognosis with high accuracy.