肝癌代谢重编程相关基因富集分析及ATP柠檬酸裂解酶表达的临床意义

目的 筛选参与肝细胞癌（HCC，简称肝癌）肿瘤进展的代谢重编程相关基因，明确HCC组织标本中ATP柠檬酸裂解酶（ACLY）表达情况，并纳入GEO数据，分析其与HCC临床病理指标的相关性及其在HCC生存预后中的作用。方法 下载TCGA数据库中的HCC表达数据，将50对癌组织与癌旁配对组织样本纳入差异表达基因分析，获得全基因表达谱列表；设置差异表达基因纳入标准，获得差异表达基因列表；通过GSEA、GO及KEGG三种富集方法筛选获得共同的HCC代谢重编程相关基因。采用qRT-PCR检测ACLY在临床组织标本中的表达情况。下载GSE14520数据集并将隶属GPL3921平台的221例生存数据完整的基因芯片表达数据和临床数据纳入研究，通过生存分析、Cox回归分析和临床相关性研究明确ACLY与HCC预后的关系。结果 通过基因富集分析筛选获得26个HCC代谢重编程相关基因。临床标本检测显示ACLY在癌组织中的表达显著高于癌旁组织（P＜0.05）。相关性分析表明ACLY表达与TNM分期、CLIP分期和AFP相关（P＜0.05）；生存分析显示ACLY的表达与HCC总体生存率相关（P＜0.05），并与HCC无复发生存有相关性趋势（P=0.05）。Cox回归分析表明ACLY的表达水平与HCC总体生存和术后无复发生存率相关（P＜0.05）。结论 本研究获得了26个HCC代谢重编程相关基因，其中ACLY的异常表达与HCC分期显著相关；ACLY的表达水平与HCC预后显著相关，是HCC总体生存的独立风险因素。

Analysis of metabolic reprogramming-related gene enrichment and the clinical significance of ATP citrate lyase expression

Objective To screen hepatocellular carcinoma (HCC) metabolic reprogramming-related genes (MRRGs) as candidates, which might be involved in oncogenesis and progression of HCC. To establish the correlation between ATP citrate lyase (ACLY) expression and HCC clinical pathological indicators and its significance on HCC survival prognosis. Methods Data from 50 pairs of tumor tissues and matched adjancent normal tissues in TCGA database was enrolled in differential expression analysis, to screen a list of whole gene expression profiles and a list of differentially expressed genes (DEGs). Then MRRGs were screened with GSEA, GO and KEGG. qRT-PCR was used to detect the expression of ACLY in tumor tissues and matched adjancent normal tissues. GSE14520 dataset was downloaded from GEO database. 221 samples belonging to GPL3921 were divided into high ACLY expression group and low ACLY expression group, the expression data and clinical data from above 221 patients were enrolled in survival analysis, Cox regression analysis, and clinicopathological analysis. Results A total of 26 HCC MRRGs were screened by differential expression analysis and gene enrichment analysis. The expression of ACLY in HCC tumors was significantly higher than that in matched adjancent normal tissues (P<0.05). Correlation analysis showed that ACLY expression was significantly related to TNM staging, CLIP staging, AFP levels in HCC (P<0.05). Survival analysis showed that ACLY expression was significantly correlated with HCC overall survival (P<0.05), and there was a trend of correlation with HCC recurrence free survival. Cox regression analysis showed that ACLY expression was significantly associated with HCC overall survival and recurrence free survival (P<0.05). Conclusion In this study, 26 genes are related to metabolic reprogramming in HCC. The expression of ACLY in tumor tissues is higher than that in adjacent normal tissues. ACLY is significantly associated with HCC tumor staging and which is an independent prognostic factor for HCC survival.