Department of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Fujian Medical University Cancer Center, Fujian Medical University, Fuzhou, Fujian, China.
Adv Ther. 2021 Jun;38(6):3342-3361. doi: 10.1007/s12325-021-01762-2. Epub 2021 May 20.
NOP58 ribonucleoprotein, a core component of box C/D small nucleolar ribonucleoproteins, is involved in various cell physiological processes. However, its role in hepatocellular carcinoma (HCC) remains very unclear. We aim to investigate NOP58 expression and its probable prognostic value in patients with HCC based on The Cancer Genome Atlas (TCGA) database.
RNA sequencing data and clinicopathological characteristics of patients with HCC were collected from TCGA database. Expression of NOP58 in HCC tissues and normal tissues was analyzed by Wilcoxon rank-sum test. Patients were divided into high and low subgroups according to median expression of NOP58. Logistic regression, gene set enrichment analysis (GSEA), and single-sample gene set enrichment analysis (ssGSEA) were conducted to annotate biological function and immune infiltration of NOP58.
NOP58 was significantly overexpressed in HCC tissues and correlated with significantly high tumor stage [odds ratio (OR) 10.01, 95% confidence interval (CI) 10.01-10.03; P = 0.003], advanced pathologic stage (OR 10.02, 95% CI 10.01-10.03; P < 0.001), advanced histologic stage (OR 10.03, 95% CI 10.02-10.04; P < 0.001), vascular invasion (OR 10.02, 95% CI 10.01-10.03; P = 0.003), poor performance status (OR 10.01, 95% CI 10.01-10.03; P = 0.003), and Mut-TP53 status (OR 10.02, 95% CI 10.01-10.03; P < 0.001). Elevated NOP58 expression had poor disease-specific survival (DSS; P < 0.001), progression-free interval (P = 0.006), and overall survival (OS; P < 0.001). NOP58 expression was independently correlated with OS (HR 1.731, 95% CI 10.037-2.890; P = 0.036). GSEA demonstrated that various cell cycle pathways along with RB-1 pathway, interleukin-10 signaling, regulation of TP53 activity, and P53 downstream pathway were differentially enriched in NOP58 high expression phenotype. NOP58 expression was positively correlated with infiltrating the levels of T helper type 2 (Th2) cells.
Overexpression of NOP58 is negatively correlated with overall survival in patients with HCC and might be a potential biomarker for prognosis of HCC.
NOP58 核糖核蛋白是 box C/D 小核仁核糖核蛋白核心成分之一，参与多种细胞生理过程。然而，其在肝细胞癌（HCC）中的作用仍不清楚。我们旨在基于癌症基因组图谱（TCGA）数据库研究 NOP58 在 HCC 患者中的表达及其可能的预后价值。
从 TCGA 数据库中收集 HCC 患者的 RNA 测序数据和临床病理特征。采用 Wilcoxon 秩和检验分析 HCC 组织和正常组织中 NOP58 的表达。根据 NOP58 的中位表达将患者分为高表达和低表达亚组。采用逻辑回归、基因集富集分析（GSEA）和单样本基因集富集分析（ssGSEA）对 NOP58 的生物学功能和免疫浸润进行注释。
NOP58 在 HCC 组织中显著过表达，与肿瘤分期较高[比值比（OR）10.01，95%置信区间（CI）10.01-10.03；P=0.003]、病理分期较晚（OR 10.02，95%CI 10.01-10.03；P<0.001）、组织学分期较晚（OR 10.03，95%CI 10.02-10.04；P<0.001）、血管侵犯（OR 10.02，95%CI 10.01-10.03；P=0.003）、较差的体能状态（OR 10.01，95%CI 10.01-10.03；P=0.003）和 Mut-TP53 状态（OR 10.02，95%CI 10.01-10.03；P<0.001）显著相关。NOP58 高表达与疾病特异性生存（DSS；P<0.001）、无进展间隔（P=0.006）和总生存（OS；P<0.001）不良显著相关。NOP58 表达与 OS 独立相关（HR 1.731，95%CI 10.037-2.890；P=0.036）。GSEA 表明，在 NOP58 高表达表型中，各种细胞周期途径以及 RB-1 途径、白细胞介素-10 信号转导、TP53 活性调节和 P53 下游途径存在差异富集。NOP58 表达与 Th2 细胞浸润水平呈正相关。
NOP58 的过表达与 HCC 患者的总生存呈负相关，可能是 HCC 预后的潜在生物标志物。
