Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006 Jiangxi Province, China.
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Avenue, Hefei, 230022 Anhui, China.
Oxid Med Cell Longev. 2022 Jun 2;2022:6891155. doi: 10.1155/2022/6891155. eCollection 2022.
Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis worldwide. However, the pathogenesis of HCC remains poorly understood. In this study, we found that NOL12 was significantly overexpressed in independent HCC datasets from TCGA database. We confirmed that the expression level of NOL12 was upregulated in human HCC tissues and cell lines by RT-qPCR. 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, knockdown of NOL12 dramatically inhibits the proliferation and metastasis of HCC cells in vitro and in vivo. CIBERSORTx analysis revealed that twelve types of tumor-infiltrating immune cells (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 immune checkpoint inhibitor (ICI) response. In conclusion, 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.
肝细胞癌(HCC)是一种常见的恶性肿瘤,全球预后较差。然而,HCC 的发病机制仍知之甚少。在这项研究中,我们发现 NOL12 在 TCGA 数据库的独立 HCC 数据集中显著过表达。我们通过 RT-qPCR 证实 NOL12 的表达水平在人 HCC 组织和细胞系中上调。NOL12 高表达与 HCC 患者总生存(OS)降低、病理分级高、淋巴结转移和临床分期晚期相关。此外,NOL12 的敲低显著抑制 HCC 细胞在体外和体内的增殖和转移。CIBERSORTx 分析显示 12 种肿瘤浸润免疫细胞(TIC)与 NOL12 表达相关。基于 8 个 NOL12 相关基因的风险特征是 HCC 患者的独立预后因素。低风险评分组患者的 OS 率优于高风险评分组。此外,高风险评分组的总肿瘤突变负担(TMB)显著增加,风险评分可作为免疫检查点抑制剂(ICI)反应的替代指标。总之,我们的研究结果表明,NOL12 可能参与 HCC 的进展,可以作为潜在的治疗靶点。此外,NOL12 相关风险特征可能与 ICI 治疗具有预测相关性。