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散在肿瘤细胞中的肿瘤相关基因表达与结直肠癌的疾病进展和肿瘤分期相关。

Tumor-associated gene expression in disseminated tumor cells correlates with disease progression and tumor stage in colorectal cancer.

作者信息

Zieglschmid Veit, Hollmann Christiane, Mannel Jenny, Albert Winfried, Jaeschke-Melli Stefan, Eckstein Birte, Hillemann Tina, Greten Tim F, Gross Eberhard, Böcher Oliver

机构信息

AdnaGen AG, Ostpassage 7, D-30853 Langenhagen, Germany.

出版信息

Anticancer Res. 2007 Jul-Aug;27(4A):1823-32.

PMID:17649779
Abstract

BACKGROUND

A possible correlation of disease progression and tumor stage in colorectal cancer patients with tumor-associated gene expression in disseminated tumor cells (DTC) was evaluated. Detection of DTC and expression of tumor-associated genes might be of clinical value with respect to individual patient prognosis, monitoring of therapy and as a surrogate tumor staging parameter.

PATIENTS AND METHODS

In a multicenter study, a total of 196 peripheral blood samples were collected from 76 patients with tumor stage Dukes' A to D and analyzed using a DTC detection assay consisting of immunomagnetic selection and expression analysis of the tumor-associated genes CEA, EGFR and GA733-2. DTC detection rates were assessed prior to surgery and post surgery in patients with tumor stage Dukes' A, B and C, and compared with results in metastatic patients. CEA serum protein levels were determined and compared with DTC and CEA expression, respectively.

RESULTS

In a comparison analysis, EGFR and CEA expression was detected in 88% (p = 0.001) and 0% (p = 0.002) prior to surgery, in 66% (p = 0.001) and 20% (p = 0.002) post surgery, as well as in 15% (p < 0.0001) and 66% (p < 0.0001) of blood samples collected from metastatic patients, respectively. Expression of tumor-associated genes in DTC prior to surgery and in follow-up samples indicated an ongoing metastatic process. DTC detection rates in patients with Dukes' A (14%), Dukes' B (13%) and Dukes' C (40%) prior to surgery correlated statistically with the expected recurrence rate. There was no correlation between DTC expressing CEA and elevation of CEA serum protein levels.

CONCLUSION

EGFR and CEA gene expression correlated with disease progression and tumor stage. Detection of CEA expression in DTC might have a predictive value in colorectal cancer and may help to identify patients at a greater risk of relapse. DTC in peripheral blood collected prior to surgery as well as in follow-up samples have a prognostic clinical value.

摘要

背景

评估了在结直肠癌患者中疾病进展与肿瘤分期和播散肿瘤细胞(DTC)中肿瘤相关基因表达之间的可能相关性。检测DTC和肿瘤相关基因的表达对于个体患者的预后、治疗监测以及作为替代肿瘤分期参数可能具有临床价值。

患者与方法

在一项多中心研究中,从76例肿瘤分期为Dukes'A至D的患者中收集了总共196份外周血样本,并使用由免疫磁珠分选和肿瘤相关基因CEA、EGFR和GA733-2的表达分析组成的DTC检测方法进行分析。在肿瘤分期为Dukes'A、B和C的患者手术前和手术后评估DTC检测率,并与转移性患者的结果进行比较。测定CEA血清蛋白水平,并分别与DTC和CEA表达进行比较。

结果

在一项比较分析中,术前EGFR和CEA表达的检测率分别为88%(p = 0.001)和0%(p = 0.002),术后分别为66%(p = 0.001)和20%(p = 0.002),从转移性患者收集的血样中分别为15%(p < 0.0001)和66%(p < 0.0001)。术前和随访样本中DTC中肿瘤相关基因的表达表明转移过程持续存在。术前Dukes'A(14%)、Dukes'B(13%)和Dukes'C(40%)患者的DTC检测率与预期复发率具有统计学相关性。表达CEA的DTC与CEA血清蛋白水平升高之间无相关性。

结论

EGFR和CEA基因表达与疾病进展和肿瘤分期相关。检测DTC中CEA的表达在结直肠癌中可能具有预测价值,并可能有助于识别复发风险较高的患者。术前及随访样本中收集的外周血中的DTC具有预后临床价值。

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