摘要
目的探究E26转录因子2(E26 oncogene homolog 2,ETS2)与肝细胞肝癌(hepatocellular carcinoma,HCC)术后复发的相关性以及其分子机制。方法利用荧光定量PCR(qRT-PCR)技术与Western blotting检测ETS2基因在HCC术后两年内复发的8例患者以及10例未复发患者癌组织样本内的表达差异。同时,利用斯皮尔曼等级相关计算ETS2表达与样本临床及病理资料间的相关性。然后利用三种交叉验证实验(留一交叉验证、十折交叉验证以及蒙特卡罗交叉验证)分析ETS2的表达对HCC样本(本研究18例样本以及ArrayExpress数据库76例样本)的术后复发预后的分型准确性。此外,进一步预测ETS2下游调控基因,并分析下游调控基因显著参与的生物学功能以及信号通路,探究ETS2可能的分子机制。结果 ETS2基因在术后复发的HCC样本中显著高表达,且其表达与血管侵袭(r=0.451,P=0.021)、有无包膜(r=0.324,P=0.047)、病理分级(r=0.422,P=0.024)以及临床分期(r=0.404,P=0.026)间存在显著的相关性。通过交叉验证实验发现ETS2对HCC样本有较好的分型准确性[本研究样本:81%(79%-82%)、78%(76%-79%)、75%(74%-76%);数据库样本:62%(59%-63%)、63%(61%-63%)、62%(60%-63%)]。通过对ETS2下游调控基因的功能富集分析发现,ETS2基因显著参与到细胞增殖、凋亡、分化以及血管增生等HCC术后发展相关的功能与通路中。结论 ETS2基因表达与血管侵袭、有无包膜、病理分级以及临床分期显著相关,两套数据的分型准确性结果说明其可做为HCC术后复发的潜在分子标记物,且其是HCC术后复发相关分子机制中重要的参与者。
Objective To explore the correlation and mechanism between E26 oncogene homolog 2 （ETS2） expression and postoperative recurrence of hepatocellular carcinoma （HCC）. Methods ETS2 expression difference between 8 postoperative recurrence of HCC patients and 10 no recurrence of HCC patients was detected by qRT-PCR and Western blotting. Meanwhile, correlation between ETS2 expression and the clinical pathological indicators were calculated by Spearman rank correlation. Then, the classified power of ETS2 for two datasets （18 samples from this study and 76 samples from ArrayExpress database） were analyzed by three cross-validation algorithms （leave-one-out cross validation （LOOCV）, 10-fold cross validation （10-fold CV）, montecarlo cross validation （MCCV）]. Moreover, the downstream genes regulated by ETS2 were predicted, and then biological functional enrichment analysis was used to detect the functions and processes related to these regulated genes. Results ETS2 gene was high expressed in postoperative recurrence of HCC patients, and significantly correlated with angiogenesis （r=0.451,P=-0.021）, tumor capsule （r=0.324, P=0.047）, pathological grade （r=0.422, P=0.024） and clinical stage （r=0.404, P=0.026）, and ETS2 had a high prediction accuracy for classified HCC [samples from this study： 81% （79%-82%）, 78% （76%-79%）, 75% （74%-76%）; samples from ArrayExpress database： 62% （59%-63%）, 63% （61%-63%）, 62% （60%-63%）]. Functional enrichment analysis showed that genes regulated by ETS2 were significantly involving in functions of cell proliferation, apoptosis, differentiation, angiogenesis and HCC progression related functions and pathways. Conclusion ETS2 expression is significantly correlated with angiogenesis, tumor capsule, pathological grade and clinical stage, which shows a great classified power for recurrence of HCC in two independent datasets, and may be biomarkers of postoperative recurrence of HCC. Moreover, ETS2 plays an important role in HCC progression.
出处
《肝胆胰外科杂志》
CAS
2016年第1期37-41,共5页
Journal of Hepatopancreatobiliary Surgery
