Wang G N, Zhang Y P, Wang M C, Han W, Zhang Y C
Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, China.
Department of Hepatopathy, Lanzhou University Second Hospital, Lanzhou 730030, China.
Zhonghua Gan Zang Bing Za Zhi. 2023 Sep 20;31(9):986-995. doi: 10.3760/cma.j.cn501113-20220108-00009.
To evaluate the role and molecular mechanism of Nei endonuclease VIII-like protein 3 (NEIL3) in hepatocellular carcinoma (HCC) through The Cancer Genome Atlas database. RNA sequencing of HCC samples was the first step in determining the level of gene NEIL3 expression in normal tissues and tumors. Then, NEIL3 was used for the Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, gene enrichment analysis, immune cell infiltration analysis. The samples were divided into high and low expression groups according to the median expression level of NEIL3 in liver cancer tissues. Logistic regression analysis, Kaplan-Meier analysis, univariate and multivariate Cox regression analysis, and a nomogram prognostic model were used to explore the clinical and prognostic significance of NEIL3 in HCC. Compared with normal samples, NEIL3 was highly expressed in most malignant tumors, including HCC ( < 0.05). High expression of NEIL3 was related to cell cycle, DNA replication, and cell receptor pathways. In addition, the high expression of NEIL3 was significantly positively correlated with T-helper 2 lymphocytes and infiltration levels ( = 0.670, < 0.001). Compared with the NEIL3 low expression group, the NEIL3 high expression group had a higher level of Th2 cell infiltration in tumor tissues ( < 0.001). Logistic regression analysis showed that NEIL3 overexpression was associated with high T stage, high pathological stage, high tissue grade, AFP > 400 μg/L and vascular invasion of HCC. The Kaplan-Meier analysis results showed that overall survival [hazard ratio () = 2.53, < 0.001)], disease-specific survival ( = 2.52, < 0.001), and progression-free interval ( = 1.82, < 0.001) in patients with HCC with high NEIL3 expression were unfavorable. Cox regression analysis results showed that high NEIL3 expression was an independent risk factor for an unfavorable prognosis in HCC patients ( = 0.002). The nomogram and calibration chart further demonstrated that high NEIL3 expression was one of the risk factors for an unfavorable prognosis in HCC patients. Elevated expression of NEIL3 is associated with an unfavorable prognosis and an increased proportion of immune cells in HCC, and it is likely to be used as a potential biomarker for evaluating the prognosis and immune infiltration level.
通过癌症基因组图谱数据库评估内核酸酶VIII样蛋白3(NEIL3)在肝细胞癌(HCC)中的作用及分子机制。对HCC样本进行RNA测序是确定正常组织和肿瘤中基因NEIL3表达水平的第一步。然后,对NEIL3进行基因本体论、京都基因与基因组百科全书、基因富集分析、免疫细胞浸润分析。根据肝癌组织中NEIL3的中位表达水平将样本分为高表达组和低表达组。采用逻辑回归分析、Kaplan-Meier分析、单因素和多因素Cox回归分析以及列线图预后模型来探讨NEIL3在HCC中的临床和预后意义。与正常样本相比,NEIL3在包括HCC在内的大多数恶性肿瘤中高表达(<0.05)。NEIL3的高表达与细胞周期、DNA复制和细胞受体途径有关。此外,NEIL3的高表达与辅助性T细胞2淋巴细胞及浸润水平显著正相关(=0.670,<0.001)。与NEIL3低表达组相比,NEIL3高表达组肿瘤组织中Th2细胞浸润水平更高(<0.001)。逻辑回归分析表明,NEIL3过表达与HCC的高T分期、高病理分期、高组织分级、AFP>400μg/L及血管侵犯有关。Kaplan-Meier分析结果显示,NEIL3高表达的HCC患者的总生存期[风险比()=2.53,<0.001]、疾病特异性生存期(=2.52,<0.001)和无进展生存期(=1.82,<0.001)均较差。Cox回归分析结果表明,NEIL3高表达是HCC患者预后不良的独立危险因素(=0.002)。列线图和校准图进一步证明,NEIL3高表达是HCC患者预后不良的危险因素之一。NEIL3表达升高与HCC患者预后不良及免疫细胞比例增加有关,很可能作为评估预后和免疫浸润水平的潜在生物标志物。