NOL12 Acts as an Oncogenic Biomarker and Predicts the Efficacy of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Abstract Background: Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis worldwide. However, the pathogenesis of HCC remains poorly understood. Methods: Through data mining and analyses of The Cancer Genome Atlas (TCGA) datasets, the NOL12 expression in HCC was determined and the associations between its expression and patient survival and clinicopathological parameters were evaluated. The pro-tumorigenic roles of NOL12 on HCC in vitro were further verified by loss-of-function assay. The correlation between NOL12 expression and tumor-infiltrating immune cells (TICs) was analyzed by CIBERSORTx method. In addition, the risk signature based on 8 NOL12-related genes was established to accurately evaluate the prognosis of patients with HCC and to further predict the efficacy of immune checkpoint inhibitors (ICIs) in HCCResults: We found that NOL12 was significantly overexpressed in independent HCC datasets from TCGA database. High expression of NOL12 is associated with worse reduced overall survival (OS), high pathological grade, node metastasis and advanced clinical stage in patients with HCC. Moreover, NOL12 knockdown significantly inhibited cell proliferation, migration and invasion. CIBERSORTx analysis revealed that twelve types of TICs are correlated with NOL12 expression. The risk signature based on 8 NOL12-related genes is an independent prognostic factor for patients with HCC. The OS rate of patients in the low-risk score group was better than that in the high-risk score group. In addition, the total tumor mutation burden (TMB) in the high-risk score group increased significantly, and the risk scores could be used as an alternative indicator of ICI response. Conclusions: Our findings indicated that NOL12 might be involved in the progression of HCC and can be used as a potential therapeutic target. Moreover, the NOL12-related risk signature may have predictive relevance with regard to ICI therapy.