Sheen I-Shyan, Jeng Kuo-Shyang, Shih Shou-Chuan, Wang Po-Chuan, Chang Wen-Hsiung, Wang Horng-Yuan, Shyung Li-Rung, Lin Shee-Chan, Kao Chin-Roa, Tsai Yi-Chun, Wu Tsu-Yen
Divisons of Hepatogastroenterology, Chang Gung Memorial Hospital, Taipei, Taiwan, China.
World J Gastroenterol. 2004 Jan;10(1):31-6. doi: 10.3748/wjg.v10.i1.31.
This study was to investigate whether surgery could increase cancer dissemination and postoperative recurrence in patients with hepatocellular carcinoma (HCC) by detection of human alpha-fetoprotein messenger RNA (hAFP mRNA). hAFP mRNA in the peripheral blood of patients with HCC has been considered as a surrogate marker for circulating tumor cells.
Eighty-one consecutive patients who underwent curative resection for HCC entered this prospective cohort study. We examined hAFP mRNA from the peripheral blood obtained preoperatively, perioperatively, and postoperatively to correlate the prognosis after curative resections from HCC patients and from the control subjects. Detection of hAFP mRNA by reverse transcriptase and polymerase chain reaction amplification (RT-PCR) was performed with primers specifically. The relations between the clinical variables (age, sex, associated liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, serum ?-fetoprotein and Child-Pugh class), the histological variables (size, capsule, vascular permeation, grade of differentiation, and daughter nodules), hAFP mRNA in peripheral blood of 3 different sessions, and postoperative course (recurrence, and recurrence related death) were analysed.
No hAFP mRNA was detected in control group subjects. Twenty-two (27%), 24 (30%) and 19 (23%) of 81 HCC patients had hAFP mRNA positivity in the preoperative, perioperative and postoperative peripheral blood. The preoperative presence did not influence the risk of HCC recurrence (55% vs 41%, P=0.280). In contrast, patients with postoperative presence had a significantly higher recurrence (90% vs 31%, P<0.001; odds ratio 19.2; 95% confidence interval: 4.0-91.7). In the multivariate analysis by COX proportional hazards model, postoperative positivity had a significant influence on recurrence (P=0.067) and recurrence related mortality (P=0.017). Whereas, the perioperative positivity of hAFP mRNA did not increase HCC recurrence (58% vs.39%, P=0.093). The correlation between perioperative hAFP mRNA positivity and recurrence related mortality had no statistical significance (P=0.836).
From our study, perioperative detection of hAFP mRNA in peripheral blood of patients has no clinical relevance and significant role in the prediction of HCC recurrence. Surgical resection itself may not accelerate cancer dissemination and does not increase postoperative recurrence significantly either.
本研究旨在通过检测人甲胎蛋白信使核糖核酸(hAFP mRNA),调查手术是否会增加肝细胞癌(HCC)患者的癌症播散及术后复发。HCC患者外周血中的hAFP mRNA已被视为循环肿瘤细胞的替代标志物。
81例连续接受HCC根治性切除术的患者进入这项前瞻性队列研究。我们检测了术前、术中和术后外周血中的hAFP mRNA,以关联HCC患者及对照者根治性切除术后的预后。使用特异性引物通过逆转录酶和聚合酶链反应扩增(RT-PCR)检测hAFP mRNA。分析临床变量(年龄、性别、合并肝硬化、乙型肝炎病毒感染、丙型肝炎病毒感染、血清甲胎蛋白及Child-Pugh分级)、组织学变量(大小、包膜、血管浸润、分化程度及子结节)、3个不同时段外周血中的hAFP mRNA与术后病程(复发及复发相关死亡)之间的关系。
对照组受试者未检测到hAFP mRNA。81例HCC患者中,分别有22例(27%)、24例(30%)和19例(23%)在术前、术中和术后外周血中hAFP mRNA呈阳性。术前hAFP mRNA阳性并不影响HCC复发风险(55%对41%,P = 0.280)。相比之下,术后hAFP mRNA阳性的患者复发率显著更高(90%对31%,P < 0.001;比值比19.2;95%置信区间:4.0 - 91.7)。在COX比例风险模型的多变量分析中,术后hAFP mRNA阳性对复发(P = 0.067)及复发相关死亡率(P = 0.017)有显著影响。而术中hAFP mRNA阳性并未增加HCC复发率(58%对39%,P = 0.093)。术中hAFP mRNA阳性与复发相关死亡率之间的相关性无统计学意义(P = 0.836)。
从我们的研究来看,术中检测患者外周血中的hAFP mRNA在预测HCC复发方面无临床相关性及显著作用。手术切除本身可能不会加速癌症播散,也不会显著增加术后复发率。