Zeng Hao, Hui Ying, Qin Wenzhou, Chen Peisheng, Huang Lifang, Zhong Wenfu, Lin Liwen, Lv Hui, Qin Xue
Department of Clinical Laboratory, Guigang City People's Hospital, Guigang, Guangxi 537100, P.R. China.
Department of Pathology, Guigang City People's Hospital, Guigang, Guangxi 537100, P.R. China.
Oncol Lett. 2020 Oct;20(4):18. doi: 10.3892/ol.2020.11879. Epub 2020 Jul 16.
Hepatitis B virus (HBV) infection is a critical factor for the initiation and progression of hepatocellular carcinoma (HCC). Gene expression profiles for HBV-associated HCC may provide valuable insight for the diagnosis and treatment of this type of HCC. The present study aimed to screen the differential genes in human HCC tissues based on high-throughput sequencing and to predict the potential therapeutic targets. Total mRNA was extracted from human HCC tissues and paracancerous tissues and sequenced using the Hiseq4000 sequencing platform. Differential gene expressions were screened and further analyzed using quantitative PCR and immunohistochemistry. A total of 2,386 differentially expressed genes were screened. Of these, 1119 were upregulated and 1,267 were downregulated in paracancerous tissues compared with tumor tissues. Gene Ontology term analysis demonstrated that differentially expressed genes were involved in carboxylic acid catabolism, monocarboxylic acid metabolic processes and α-amino acid metabolic processes. Molecular functional analysis revealed that the differentially expressed genes functioned in oxidoreductase activity, for example acting on CH-OH group of donors and permitting identical protein binding, anion binding, coenzyme binding and monocarxylic acid transporter activity. The Kyoto Encyclopedia of Genes and Genomes analysis reported that the differentially expressed genes were primarily concentrated in 20 signaling pathways, such as valine, leucine and leucine degradation, retinol metabolism and the cell cycle. Differential expression of proteins regulating the cell cycle, including stratifin, cyclin B1 and cyclin-dependent kinase 1, were significantly higher in tumor tissue compared with those in paracancerous tissue at both the mRNA and protein levels. These results were consistent with those obtained from high-throughput sequencing, indicating the reliability of the high-throughput sequencing. Together, these results identified differentially expressed genes and predicted the subsequent signaling pathways, which may be involved in the occurrence and development of HCC. Therefore, the present study may provide novel implications in the therapeutic and diagnosis of HCC.
乙型肝炎病毒（HBV）感染是肝细胞癌（HCC）发生和发展的关键因素。HBV相关HCC的基因表达谱可能为这类HCC的诊断和治疗提供有价值的见解。本研究旨在基于高通量测序筛选人HCC组织中的差异基因，并预测潜在的治疗靶点。从人HCC组织和癌旁组织中提取总mRNA，并使用Hiseq4000测序平台进行测序。筛选差异基因表达，并使用定量PCR和免疫组织化学进行进一步分析。共筛选出2386个差异表达基因。其中，与肿瘤组织相比，癌旁组织中有1119个基因上调，1267个基因下调。基因本体论术语分析表明，差异表达基因参与羧酸分解代谢、单羧酸代谢过程和α-氨基酸代谢过程。分子功能分析显示，差异表达基因具有氧化还原酶活性，例如作用于供体的CH-OH基团，并具有相同蛋白质结合、阴离子结合、辅酶结合和单羧酸转运蛋白活性。京都基因与基因组百科全书分析报告称，差异表达基因主要集中在20条信号通路中，如缬氨酸、亮氨酸和异亮氨酸降解、视黄醇代谢和细胞周期。在mRNA和蛋白质水平上，与癌旁组织相比，肿瘤组织中调节细胞周期的蛋白质（包括层粘连蛋白、细胞周期蛋白B1和细胞周期蛋白依赖性激酶1）的差异表达明显更高。这些结果与高通量测序获得的结果一致，表明高通量测序的可靠性。总之，这些结果鉴定了差异表达基因并预测了后续的信号通路，这些可能与HCC的发生和发展有关。因此，本研究可能为HCC的治疗和诊断提供新的启示。
