肝癌组织和细胞系EGFL8基因表达及其临床意义

目的表皮生长因子样结构域8(epidermal growth factor-like domain 8,EGFL8)在多种癌症中表达失调且与患者的不良预后相关,但关于EGFL8在肝细胞癌组织表达尚不清楚。本研究旨在探讨EGFL8基因在肝癌组织及细胞系中表达水平并分析其临床意义。方法收集2014-02-01-2016-02-01暨南大学附属广州市红十字会医院行手术切除的42例肝癌患者标本及其对应的癌旁肝组织标本(距原发癌边缘>2cm)。培养HCCLM3、SMMC-7721、HepG2及Hep3B等4种具有不同侵袭转移潜能的肝癌细胞系和HL-7702正常肝细胞系,采用荧光实时定量PCR方法检测EGFL8基因在上述组织标本及细胞系中的表达量,并分析EGFL8基因表达与肝癌临床病理特征及侵袭转移潜能之间的相关性。结果 EGFL8基因在肝癌组织中的平均表达量(0.006 5±0.001 8)低于相应的癌旁肝组织(0.020 0±0.005 2),差异有统计学意义,U=425,P=0.015。且EGFL8基因表达下调与肝癌的静脉侵犯(χ~2=7.860,P=0.060)、多结节(χ~2=5.316,P=0.011)及较晚的TNM分期(χ~2=6.035,P=0.014)密切相关。EGFL8基因在肝癌细胞系中的表达量均低于正常肝细胞系(F=155.900,P=0.001),且其在高侵袭转移潜能肝癌细胞系中的表达量(0.000 26±0.000 03)低于低侵袭转移潜能的肝癌细胞系(0.001 36±0.000 12),P<0.001。结论 EGFL8在肝癌组织及细胞系中的表达水平明显下调,且其表达下调与肝癌的侵袭转移潜能、疾病进展及不良预后密切相关,提示EGFL8是一个潜在的肝癌分子标志物。

Expression of EGFL8 gene in hepatocellular carcinoma tissues and cell lines and its clinical significance

OBJECTIVE Epidermal growth factor-like domain 8 is dysregulated in a variety of cancers and is associated with poor patient prognosis,but the expression of EGFL8 in hepatocellular carcinoma(HCC)is unclear.The purpose of this study was to investigate the expression level of EGFL8 gene in hepatocellular carcinoma tissues and cell lines and analyze its clinical significance.METHODS Collected 42 fresh liver cancer specimens and their corresponding adjacent liver tissue specimens(>2 cm from the edge of the primary cancer)for surgical resection at Guangzhou Red Cross Hospital from February 01,2014 to February 01,2016.Cultivate 4 types of HCCLM3,SMMC-7721,HepG2 and Hep3 Bhepatocellular carcinoma cell lines with different invasion and metastatic potential and HL-7702 normal hepatic cell line.Real-time quantitative PCR was used to detect the expression of EGFL8 gene in the above tissue samples and cell lines,and the correlation between EGFL8 gene expression and clinicopathological characteristics and invasion and metastasis potential of HCC.RESULTS The average expression of EGFL8 gene in hepatocellular carcinoma tissues(0.006 5±0.001 8)was lower than that in corresponding adjacent cancer tissues(0.020 0±0.005 2,U=425,P=0.015),the down-regulation of EGFL8 was associated with venous invasion(χ~2=7.860,P=0.060),multiple nodules(χ~2=5.316,P=0.011),and high TNM stage(χ~2=6.035,P=0.014).The expression level of EGFL8 gene in hepatocellular carcinoma cell lines was lower than that in normal hepatic cell line,and its expression level in hepatocellular carcinoma cell lines with high invasion and metastatic potential was lower than that in cell lines with low invasion and metastatic potential(F=155.900,P=0.001).CONCLUSION The expression of EGFL8 in hepatocellular carcinoma tissues and cell lines is significantly downregulated,and its down-regulation is closely related to the invasion and metastasis potential,disease progression and poor prognosis of HCC,suggesting that EGFL8 is a potential molecular marker of HCC.