Identification of a bile acid and bile salt metabolism-related lncRNA signature for predicting prognosis and treatment response in hepatocellular carcinoma

Abstract

Abstract Bile acids and salts have been shown to play a role in liver carcinogenesis through DNA damage, inflammation, and tumor proliferation. However, the correlation between bile acid metabolism and hepatocellular carcinoma (HCC) prognosis remains unclear. This study aimed to identify a predictive signature of bile acid and bile salt metabolism-related long non-coding RNAs (lncRNAs) for HCC prognosis and treatment response. The study used HCC RNA-sequencing data and corresponding clinical and prognostic data from The Cancer Genome Atlas. A prognostic model consisting of five bile acid and bile salt metabolism-related lncRNAs was developed and evaluated in a training set, a validation set and an external set. The model demonstrated good performance in predicting HCC prognosis and was shown to be an independent biomarker for prognosis. Additionally, our study revealed a significant association between the signature and immune cell infiltration, as well as its predictive value for therapeutic responses to both immunotherapy and chemotherapy. Furthermore, three LncRNAs (LUCAT1, AL031985.3 and AC015908.3) expression levels in our signature were validated through qRT-PCR in a cohort of 50 pairs of HCC patient tumor samples and corresponding adjacent non-tumor samples, along with 10 samples of normal liver tissue adjacent to benign lesions. These findings suggest that this novel bile acid and bile salt metabolism-related lncRNA signature can independently predict the prognosis of patients with HCC and may be utilized as a potential predictor of response to treatment in this setting.