Department of Infectious Disease, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, Nanning, Guangxi.
College of Health and Rehabilitation, Chengdu University of Chinese Medicine, Chengdu, Sichuan, PR China.
Medicine (Baltimore). 2021 Jan 15;100(2):e24172. doi: 10.1097/MD.0000000000024172.
Hepatocellular carcinoma (HCC) is the cause of an overwhelming number of cancer-related deaths across the world. Developing precise and noninvasive biomarkers is critical for diagnosing HCC. Our research was designed to explore potentially useful biomarkers of host peripheral blood mononuclear cell (PBMC) in HCC by integrating comprehensive bioinformatic analysis.
Gene expression data of PBMC in both healthy individuals and patients with HCC were extracted from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs). The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to annotate the function of DEGs. Protein-protein interaction analysis was performed to screen the hub genes from DEGs. cBioportal database analysis was performed to assess the prognostic significance of hub genes. The Cancer Cell Line Encyclopedia (CCLE) and The Human Protein Atlas (HPA) database analyses were performed to confirm the expression levels of the hub genes in HCC cells and tissue.
A total of 95 DEGs were screened. Results of the GO analysis revealed that DEGs were primarily involved in platelet degranulation, cytoplasm, and protein binding. Results of the KEGG analysis indicated that DEGs were primarily enriched in focal adhesion. Five genes, namely, myosin light chain kinase (MYLK), interleukin 1 beta (IL1B), phospholipase D1 (PLD1), cortactin (CTTN), and moesin (MSN), were identified as hub genes. A search in the CCLE and HPA database showed that the expression levels of these hub genes were remarkably increased in the HCC samples. Survival analysis revealed that the overexpression of MYLK, IL1B, and PLD1 may have a significant effect on HCC survival. The aberrant high expression levels of MYLK, IL1B, and PLD1 strongly indicated worse prognosis in patients with HCC.
The identified hub genes may be closely linked with HCC tumorigenicity and may act as potentially useful biomarkers for the prognostic prediction of HCC in PBMC samples.
肝细胞癌（HCC）是全球范围内导致大量癌症相关死亡的主要原因。开发准确且非侵入性的生物标志物对于 HCC 的诊断至关重要。我们的研究旨在通过整合综合生物信息学分析来探索宿主外周血单个核细胞（PBMC）中可能有用的 HCC 生物标志物。
从基因表达综合数据库（GEO）中提取健康个体和 HCC 患者 PBMC 的基因表达数据，以鉴定差异表达基因（DEGs）。对 DEGs 进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析，以注释 DEGs 的功能。进行蛋白质-蛋白质相互作用分析，从 DEGs 中筛选枢纽基因。通过 cBioportal 数据库分析评估枢纽基因的预后意义。通过癌症细胞系百科全书（CCLE）和人类蛋白质图谱（HPA）数据库分析确认 HCC 细胞和组织中枢纽基因的表达水平。
共筛选出 95 个 DEGs。GO 分析结果表明，DEGs 主要参与血小板脱颗粒、细胞质和蛋白质结合。KEGG 分析结果表明，DEGs 主要富集在焦点黏附。鉴定出 5 个基因，即肌球蛋白轻链激酶（MYLK）、白细胞介素 1β（IL1B）、磷脂酶 D1（PLD1）、皮质蛋白（CTTN）和膜突蛋白（MSN），作为枢纽基因。在 CCLE 和 HPA 数据库中搜索表明，这些枢纽基因在 HCC 样本中的表达水平显著增加。生存分析表明，MYLK、IL1B 和 PLD1 的过表达可能对 HCC 生存有显著影响。MYLK、IL1B 和 PLD1 的异常高表达强烈表明 HCC 患者的预后较差。
鉴定出的枢纽基因可能与 HCC 肿瘤发生密切相关，并且可能作为 PBMC 样本中 HCC 预后预测的潜在有用生物标志物。
