Xu Shaohua, Gao Ruihuan, Zhou Yidan, Yang Ying, Zhang Yi, Li Qianyuan, Luo Chunhua, Liu Song-Mei
Department of Clinical Laboratory, Center for Gene Diagnosis & Program of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, China.
The First College of Clinical Medical Science, Three Gorges University, Hubei, China.
Front Oncol. 2022 Jun 20;12:862216. doi: 10.3389/fonc.2022.862216. eCollection 2022.
Primary liver cancer is still the most common lethal malignancy. The N-myc downstream-regulated gene family () is a group of multifunctional proteins associated with carcinogenesis. However, systematic evaluation of the diagnostic and prognostic values of or expression in liver cancer is poorly investigated.
The gene expression matrix of liver hepatocellular carcinoma (LIHC) was comprehensively analyzed by the "limma" and "Dseq2" R packages. The Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) were used to identify the biological functional differences. A single-sample GSEA (ssGSEA) was conducted to quantify the extent of immune cell infiltration. Finally, the clinical and prognostic information of LIHC patients was systematically investigated using Kaplan-Meier analysis and logistic and Cox regression analysis.
Compared with normal tissues, expression was higher, whereas expression was lower in tumor tissues (0.001). The area under the receiver operator characteristic curve (AUROC) of and for LIHC was 0.715 and 0.799, respectively. Kaplan-Meier analysis revealed that and were independent clinical prognostic biomarkers for the overall survival (OS, = 0.001 and 2.9e-06), progression-free interval (PFI, = 0.028 and 0.005) and disease-specific survival (DSS, = 0.027 and 0.001). The C-indexes and calibration plots of the nomogram suggest that and have an effective predictive performance for OS (C-index: 0.676), DSS (C-index: 0.741) and PFI (C-index: 0.630) of liver cancer patients. The mutation rate of in liver cancer reached up to 14%, and DNA methylation levels of and promoters correlated significantly with clinical prognosis.
The mRNA expression and DNA methylation of superfamily members have the potential for LIHC diagnosis and prognosis integrative analysis from multiple cohorts.
原发性肝癌仍是最常见的致命恶性肿瘤。N - myc下游调控基因家族（）是一组与致癌作用相关的多功能蛋白。然而，对该家族基因在肝癌中的诊断和预后价值的系统评估研究较少。
通过“limma”和“Dseq2”R软件包全面分析肝细胞癌（LIHC）的基因表达矩阵。利用基因本体论（GO）和基因集富集分析（GSEA）来识别生物学功能差异。进行单样本GSEA（ssGSEA）以量化免疫细胞浸润程度。最后，使用Kaplan - Meier分析以及逻辑回归和Cox回归分析系统地研究LIHC患者的临床和预后信息。
与正常组织相比，肿瘤组织中该家族某基因表达较高，而另一基因表达较低（P < 0.001）。LIHC中该家族这两个基因的受试者工作特征曲线下面积（AUROC）分别为0.715和0.799。Kaplan - Meier分析显示，这两个基因是总生存期（OS，P = 0.001和2.9e - 06）、无进展生存期（PFI，P = 0.028和0.005）和疾病特异性生存期（DSS，P = 0.027和0.001）的独立临床预后生物标志物。列线图的C指数和校准图表明，这两个基因对肝癌患者的OS（C指数：0.676）、DSS（C指数：0.741）和PFI（C指数：0.630）具有有效的预测性能。肝癌中该家族某基因的突变率高达14%，该家族另外两个基因启动子的DNA甲基化水平与临床预后显著相关。
该家族成员的mRNA表达和DNA甲基化在多队列LIHC诊断和预后综合分析中具有潜在价值。
