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The analysis of clinical importance of circulating cancer cells in the peripheral blood spread from primary tumors of the digestive organs during surgical manipulation.

手术操作过程中消化器官原发性肿瘤扩散的外周血循环癌细胞的临床重要性分析。

基本信息

批准号：
15591406
负责人：
IKEGUCHI Masahide
金额：
$ 1.79万
依托单位：
National University Corporation Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

In detection of cancer cells in the blood or in the peritoneal washings by real-time RT-PCR method, CEA mRNA was found as most sensitive and reliable marker than cytokeratins. Total RNA was extracted from 1.5 ml of peripheral blood from 59 patients with gastric cancer and 15 patients with cholecystolithiasis (control) before and after operation. CEA was used as a probe to detect gastric cancer cells in samples using a real-time RT-PCR. As results, CEA mRNA positive cells were not found in the peripheral blood of the control patients either before or after operation, nor in the peripheral blood of the gastric cancer patients before operation. However, CEA mRNA positive cells were detected in 46% of the patients just after gastrectomy, though these circulating cancer cells disappeared from peripheral blood within 2 post-operative days. In 55 patients who underwent a curative operation, the risk for cancer recurrence (10/30;33%) in 30 patients who did not show circulating cancer cells postoperatively was higher than that for cancer recurrence (3/25;12%) in 25 patients with positive for circulating cancer cells (p=0.064). As a result, the presence of blood circulating tumor cells just after surgery tends to correlate with a low rate of tumor recurrence in patients operated on for gastric cancer. These findings indicate that a gastrectomy may spread gastric cancer cells into the peripheral blood from primary tumors, however, such circulating cancer cells may be destroyed within a short time. The detection of circulating cancer cells may therefore be a marker for a possibly better prognosis in patients with gastric cancer. Moreover, intraperitoneal chemotherapy(IPC) effectiveness may correlate with elevation of gene expression of inflammatory cytokines, such as IL-2 and IL-6 in the peritoneal cavity after IPC. However, the prognostic benefits of IPC for scirrhous gastric cancer(SGC) patients remains unclear.

在用实时荧光定量RT-PCR方法检测血液或腹腔冲洗液中的癌细胞时，发现CEA mRNA是比细胞角蛋白更敏感和可靠的标记物。从59例胃癌患者和15例胆囊结石患者（对照组）手术前后的外周血中提取总RNA 1.5ml。以CEA为探针，采用实时荧光定量RT-PCR检测胃癌细胞。结果：正常对照组患者术前、术后外周血中均未发现CEA mRNA阳性细胞，胃癌患者术前外周血中也未发现CEA mRNA阳性细胞。然而，在46%的患者在胃切除术后立即检测到CEA mRNA阳性细胞，尽管这些循环癌细胞在术后2天内从外周血中消失。在55例接受根治性手术的患者中，术后未显示循环癌细胞的30例患者的癌症复发风险（10/30;33%）高于循环癌细胞阳性的25例患者的癌症复发风险（3/25;12%）（p=0.064）。因此，手术后血液循环肿瘤细胞的存在往往与胃癌手术患者的低肿瘤复发率相关。这些发现表明，胃切除术可能会将胃癌细胞从原发性肿瘤扩散到外周血中，然而，这种循环癌细胞可能会在短时间内被破坏。因此，循环癌细胞的检测可能是胃癌患者预后可能更好的标志。此外，腹膜内化疗（IPC）的有效性可能与IPC后腹腔中炎性细胞因子（如IL-2和IL-6）的基因表达升高相关。然而，IPC对硬化性胃癌（SGC）患者的预后益处仍不清楚。