Mou D-C, Cai S-L, Peng J-R, Wang Y, Chen H-S, Pang X-W, Leng X-S, Chen W-F
Center of Hepatobiliary Surgery, People's Hospital, Peking University Health Science Center, 42 Beilishilu, Beijing 100044, China.
Br J Cancer. 2002 Jan 7;86(1):110-6. doi: 10.1038/sj.bjc.6600016.
The members of MAGE gene family are highly expressed in human hepatocellular carcinoma (HCC). In the present study, we tested the tumour-specific MAGE-1 and MAGE-3 transcripts in the peripheral blood of HCC patients by nested RT-PCR to detect the circulating tumour cells and evaluate their potential clinical implication. Of 30 HCC patients, the positive rate of MAGE-1 and MAGE-3 transcripts was 43.3% (13 out of 30) and 33.3% (10 out of 30) in PBMC samples, whilst the positive rate was 70% (21 out of 30) and 53.3% (16 out of 30) in the resected HCC tissue samples, respectively. The positivity for at least one MAGE gene transcript was 63.3% (19 out of 30) in PBMC samples of HCC patients and 83.3% (25 out of 30) in the resected HCC tissue samples. MAGE-1 and/or MAGE-3 mRNA were not detected in the PBMC of those patients from whom the resected HCC tissues were MAGE-1 or MAGE-3 mRNA negative, nor in the 25 PBMC samples from healthy donors. The detection of MAGE transcripts in PBMC was correlated with the advanced stages and tumour size of the HCC, being 82.4% (14 out of 17) in tumour stages III and IVa, 56.6% (five out of nine) in stage II, and null (nought out of four) in stage I. The serum alpha-FP in 33.3% (10 out of 30) of HCC patients was normal or slightly elevated (< 40 ng ml(-1)). However, six of these 10 patients (alpha-FP < 40 ng ml(-1)) were MAGE-1 and /or MAGE-3 mRNA positive in their PBMC. The follow-up survey of MAGE mRNA in PBMC was performed in 12 patients. Seven patients with persistent MAGE-1 and/or MAGE-3 mRNA positive or from negative turned to positive died because of metastasis and/or recurrence. In striking contrast, all four patients with MAGE-1 and/or MAGE-3 mRNA from positive turned to negative and one patient with persistent MAGE-3 transcript negative are alive after last test. Collectively, detection of MAGE transcripts with follow-up survey in PBMC is a feasible and reliable assay for the early prediction of the relapse and prognosis of the HCC patients.
MAGE基因家族成员在人类肝细胞癌（HCC）中高表达。在本研究中，我们通过巢式逆转录聚合酶链反应（nested RT-PCR）检测HCC患者外周血中肿瘤特异性的MAGE-1和MAGE-3转录本，以检测循环肿瘤细胞并评估其潜在的临床意义。30例HCC患者中，外周血单个核细胞（PBMC）样本中MAGE-1和MAGE-3转录本的阳性率分别为43.3%（30例中的13例）和33.3%（30例中的10例），而在切除的HCC组织样本中，阳性率分别为70%（30例中的21例）和53.3%（30例中的16例）。HCC患者PBMC样本中至少一种MAGE基因转录本的阳性率为63.3%（30例中的19例），切除的HCC组织样本中的阳性率为83.3%（30例中的25例）。在切除的HCC组织为MAGE-1或MAGE-3 mRNA阴性的患者的PBMC中，以及在25份健康供体的PBMC样本中，均未检测到MAGE-1和/或MAGE-3 mRNA。PBMC中MAGE转录本的检测与HCC的晚期阶段和肿瘤大小相关，在肿瘤III期和IVa期为82.4%（17例中的14例），II期为56.6%（9例中的5例），I期为零（4例中的0例）。33.3%（30例中的10例）的HCC患者血清甲胎蛋白（alpha-FP）正常或略有升高（<40 ng ml-1）。然而，这10例患者中有6例（alpha-FP<40 ng ml-1）的PBMC中MAGE-1和/或MAGE-3 mRNA呈阳性。对12例患者的PBMC中的MAGE mRNA进行了随访调查。7例MAGE-1和/或MAGE-3 mRNA持续阳性或由阴性转为阳性的患者因转移和/或复发死亡。形成鲜明对比的是，所有4例MAGE-1和/或MAGE-3 mRNA由阳性转为阴性的患者以及1例MAGE-3转录本持续阴性的患者在最后一次检测后仍存活。总体而言，PBMC中MAGE转录本的检测及随访调查是早期预测HCC患者复发和预后的一种可行且可靠的检测方法。
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