Low Expression is Associated with Poor Prognosis in Hepatocellular Carcinoma.

AT-rich interactive domain 1A () is one of the most frequently mutated genes in hepatocellular carcinoma (HCC), but its clinical significance is not clarified. We aimed to evaluate the clinical significance of low expression in HCC. By analyzing the gene expression data of liver from -knockout mice, hepatic -specific gene expression signature was identified ( < 0.05 and 0.5-fold difference). From this signature, a prediction model was developed to identify tissues lacking activity and was applied to gene expression data from three independent cohorts of HCC patients to stratify patients according to activity. The molecular features associated with loss of were analyzed using The Cancer Genome Atlas (TCGA) multi-platform data, and Ingenuity Pathway Analysis (IPA) was done to uncover potential signaling pathways associated with loss. inactivation was clinically associated with poor prognosis in all three independent cohorts and was consistently related to poor prognosis subtypes of previously reported gene signatures (highly proliferative, hepatic stem cell, silence of Hippo pathway, and high recurrence signatures). Immune activity, indicated by significantly lower IFNG6 and cytolytic activity scores and enrichment of regulatory T-cell composition, was lower in the -low subtype than -high subtype. Ingenuity pathway analysis revealed that direct upstream transcription regulators of the signature were genes associated with cell cycle, including group, and while tumor suppressors such as and were significantly inhibited. plays an important role in immune activity and regulating multiple genes involved in HCC development. Low- subtype was associated with poor clinical outcome and suggests the possibility of as a prognostic biomarker in HCC patients.