Yang Shi-zhong, Dong Jia-hong, Zhu Jin, Li Kun, Zhang Yu
Department of Hepatobiliary Surgery, Institute of Hepatobiliary Surgery, First Affiliated Hospital, Third Military Medical University, Chongqing 400038, China.
Zhonghua Wai Ke Za Zhi. 2004 Sep 7;42(17):1060-3.
To explore the feasibility of alpha-fetoproteins (alpha-FP) mRNA and melanoma antigen-1 (MAGE-1) mRNA as 2 markers of micrometastasis in hepatocellular carcinoma (HCC) patients' peripheral blood.
Subjects were divided into five groups: patients with HCC (n=65); patients with hepatitisB and liver cirrhosis (n=22); patients with metastatic liver cancer (n=12); patients with hepatic hemangioma (n=12); and healthy volunteers (n=20). alpha-FP mRNA and MAGE-1 mRNA in peripheral blood were tested by nested reverse transcription polymerase chain reaction (RT-PCR).
MAGE-1 mRNA and alpha-FP mRNA were detected in 27 (42%) and 35 (54%) of 65 HCC patients respectively, while 42 (65%) HCC patients were positive for at least 1 marker. The frequency of alpha-FP mRNA and MAGE-1 mRNA positivity strongly correlated with portal thrombosis, intrahepatic metastatic nodules, tumor diameter and TNM stage (P <0.05). With regard to controls, 4 of 12 (33%) samples from patients with metastatic liver cancer showed MAGE-1 mRNA in their peripheral blood, but groups of hepatitis and cirrhosis, hepatic hemangioma, healthy volunteers did not. And 3 of 22 samples (14%) from group hepatitis and cirrhosis showed alpha-FP mRNA, but none of samples from other control group showed alpha-FP mRNA.
Nested RT-PCR is a sensitive and reliable method for detecting circulating HCC cells. Two-marker RT-PCR assay with a liver-specific alpha-FP marker in combination with a cancer-specific MAGE-1 marker may be a promising tool for detecting micrometastases with better sensitivity and specificity than one marker RT-PCR.
探讨甲胎蛋白(α-FP)信使核糖核酸(mRNA)和黑色素瘤抗原-1(MAGE-1)mRNA作为肝细胞癌(HCC)患者外周血微转移的2种标志物的可行性。
将受试者分为5组:HCC患者(n = 65);乙型肝炎和肝硬化患者(n = 22);转移性肝癌患者(n = 12);肝血管瘤患者(n = 12);健康志愿者(n = 20)。采用巢式逆转录聚合酶链反应(RT-PCR)检测外周血中的α-FP mRNA和MAGE-1 mRNA。
65例HCC患者中,分别有27例(42%)和35例(54%)检测到MAGE-1 mRNA和α-FP mRNA,而42例(65%)HCC患者至少有1种标志物呈阳性。α-FP mRNA和MAGE-1 mRNA阳性频率与门静脉血栓形成、肝内转移结节、肿瘤直径和TNM分期密切相关(P <0.05)。在对照组中,12例转移性肝癌患者的4份样本(33%)外周血中检测到MAGE-1 mRNA,而肝炎和肝硬化组、肝血管瘤组、健康志愿者组均未检测到。肝炎和肝硬化组22份样本中有3份(14%)检测到α-FP mRNA,而其他对照组样本均未检测到α-FP mRNA。
巢式RT-PCR是检测循环HCC细胞的一种灵敏可靠的方法。采用肝脏特异性α-FP标志物与癌症特异性MAGE-1标志物联合的双标志物RT-PCR检测法,可能是一种比单标志物RT-PCR检测微转移具有更高灵敏度和特异性的有前景的工具。