Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Department of Interventional Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Sci Prog. 2021 Jul-Sep;104(3):368504211031749. doi: 10.1177/00368504211031749.
This integrated bioinformatic study aimed to investigate potential prognostic candidates in hepatocellular carcinoma (HCC). In the GSE14520, GSE101685, and The Cancer Genome Atlas (TCGA) datasets, differentially expressed genes (DEGs) were identified and functional pathways of common DEGs were enriched. The least absolute shrinkage and selection operator (LASSO) model was used to screen the potential parameters associated with overall survival (OS) in HCC patients. Metabolic pathways were the most significantly enriched functional pathways of common DEGs in these three datasets. After LASSO model analysis, HMGCS2, UGP2, BCLC staging and TNM staging were screened as potential prognostic candidates for OS in HCC patients in GSE14520. HMGCS2 in the metabolic pathway was significantly downregulated in tumor tissues and peripheral blood mononuclear cells in HCC patients (all < 0.05). Cox regression model indicated that HMGCS2 might be associate with OS in HCC patients in GSE14520 and in the TCGA ( = 0.029 and = 0.05, respectively). Kaplan-Meier analysis demonstrated that HMGCS2 downregulation in tumors contributed to an unfavorable OS in HCC patients, both in GSE14520 and in the TCGA ( = 0.0001 and = 0.0002, respectively). Additionally, HMGCS2 was significantly downregulated in HCC patients with high alpha-fetoprotein (AFP), main tumor size >5 cm, multinodular, advanced tumor staging including BCLC, TNM and CLIP (all < 0.05). HMGCS2 was involved in metabolic pathways, and downregulated HMGCS2 in tumors was associated with unfavorable OS in HCC patients.
本综合生物信息学研究旨在探讨肝细胞癌（HCC）潜在的预后候选标志物。在 GSE14520、GSE101685 和癌症基因组图谱（TCGA）数据集，鉴定差异表达基因（DEGs），并对共同 DEGs 的功能途径进行富集分析。使用最小绝对收缩和选择算子（LASSO）模型筛选与 HCC 患者总生存期（OS）相关的潜在参数。在这三个数据集，共同 DEGs 的代谢途径是最显著富集的功能途径。LASSO 模型分析后，在 GSE14520 中筛选 HMGCS2、UGP2、BCLC 分期和 TNM 分期作为 HCC 患者 OS 的潜在预后标志物。在 HCC 患者肿瘤组织和外周血单核细胞中，HMGCS2 在代谢途径中显著下调（均 < 0.05）。Cox 回归模型表明，在 GSE14520 和 TCGA 中，HMGCS2 可能与 HCC 患者的 OS 相关（= 0.029 和 = 0.05）。Kaplan-Meier 分析表明，在 GSE14520 和 TCGA 中，肿瘤中 HMGCS2 的下调与 HCC 患者的不利 OS 相关（= 0.0001 和 = 0.0002）。此外，在 AFP 高、主肿瘤直径 >5cm、多结节、BCLC、TNM 和 CLIP 等肿瘤分期较晚的 HCC 患者中，HMGCS2 明显下调（均 < 0.05）。HMGCS2 参与代谢途径，肿瘤中下调的 HMGCS2 与 HCC 患者的不利 OS 相关。
