目的: 研究二氢硫辛酰胺转乙酰基酶（dihydrolipoamide S-acetyltransferase,DLAT）在肝细胞癌（HCC）中的表达和预后价值,为HCC的预后评估和药物治疗提供新的生物标志物。方法: 通过生物信息学分析DLAT在HCC中的表达、预后价值以及相关生物学功能。收集湖南省人民医院50例HCC患者的临床病理资料,采用免疫组化分析DLAT在肿瘤组织和癌旁组织中的差异表达,并进一步分析DLAT的预后价值。q-PCR检查HCC细胞系HepG2、Huh-7、SMMC-7721和人正常肝组织细胞系LO2中DLAT mRNA的表达。在HepG2细胞中转染si-DLAT（实验组）和si-NC（对照组）,CCK8实验和流式细胞术检测DLAT对细胞增殖和凋亡的影响。结果: DLAT在HCC组织中的表达高于正常组织,并与患者预后不良呈正相关。DLAT在HCC中的高表达与免疫细胞浸润水平和细胞周期调控基因密切相关。沉默DLAT后,HepG2细胞的增殖明显慢于对照组,凋亡比例高于对照组。结论: DLAT可作为HCC患者良好的预后标志物,并可能成为治疗HCC的新靶点。
Abstract
Objective The aim of this study is to investigate the expression and prognostic value of dihydrolipoamide S-acetyltransferase(DLAT) in hepatocellular carcinoma (HCC), and to provide a new biomarker for prognosis evaluation and drug therapy of HCC. Methods The expression, prognostic value and related biological function of DLAT in HCC were analyzed by bioinformatics. Then, the clinicopathological data of 50 HCC patients from Hunan Provincial People's Hospital were collected. The differential expression of DLAT in tumor tissues and adjacent tissues was analyzed by immunohistochemistry, and the prognostic value of DLAT was further analyzed. HCC cell lines HepG2, Huh-7, SMMC-7721 and human normal liver tissue cell line LO2 were cultured, and the expression of DLAT mRNA in each cell line was detected by q-PCR. HepG2 cells were transfected with si-DLAT (experimental group) and si-NC (control group), and CCK8 assay and flow cytometry were used to detect the effect of DLAT on cell proliferation and apoptosis. Results The expression of DLAT in HCC tissues is higher than that in normal tissues, and expression level of DLAT are positively correlated with poor prognosis. The high expression of DLAT in HCC is closely related to the level of immune cell infiltration and cell cycle regulatory genes. After silencing DLAT, the proliferation of HepG2 cells was significantly slower than that of the control group, and the proportion of apoptosis was higher than that of the control group. Conclusion DLAT can be used as a good prognostic marker for patients with HCC, and may become a new target for the treatment of HCC.
关键词
肝细胞癌 /
二氢硫辛酰胺转乙酰基酶 /
预后标志物
Key words
hepatocellular carcinoma /
dihydrolipoamide S-acetyltransferase(DLAT) /
prognostic biomarker
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基金
湖南省教育厅资助项目“术前全身免疫炎症指数与肝细胞癌微血管侵犯及预后的相关分析”（21c0047）
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