Tunca Berrin, Egeli Unal, Cecener Gulsah, Tezcan Gulcin, Gökgöz Sehsuvar, Tasdelen Ismet, Bayram Nuran, Tolunay Sahsine, Umut Gorkem, Demirdogen Elif, Erturk Elif, Ak Secil, Cetintas Sibel, Evrensel Turkkan
Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
Tumori. 2012 Mar-Apr;98(2):243-51. doi: 10.1177/030089161209800211.
The major cause of death in breast cancer patients is metastasis. Various biomarkers have been used for the early detection of circulating tumor cells in the peripheral blood of breast cancer patients. The aims of the current study were to analyze circulating tumor cells in the blood of breast cancer patients by investigating EGFR, CK19, CK20 and HER2 expression profiles and to evaluate their prognostic importance.
CK19, CK20 and EGFR gene expression profiles were evaluated in the blood samples of 84 female patients with primary invasive ductal breast cancer and 20 healthy female volunteers using SYBR green-based real-time qPCR assays. HER2 expression analyses were conducted in 46 patients who had an HER2-positive primary tumor and in 30 healthy women to determine the cutoff level of positivity.
The positive rates of CK20, EGFR, CK19 and HER2 mRNA expression in the peripheral blood were 28.57% (24/84), 20.23% (17/84), 5.95% (5/84) and 2.17% (1/46), respectively. The high positive ratio of CK20 mRNA expression in the peripheral blood of breast cancer was identified for the first time in the current study. Significant differences were identified in CK20 expression status and several clinical parameters related with aggressiveness of tumors using a binary logistic regression analysis. Higher CK20-positive levels were observed in patients who had lymph node metastasis and advanced-grade primary tumors, which were estrogen receptor-negative. We have demonstrated that CK20 may be a novel biomarker that is useful to identify circulating tumor cells and predict breast cancer progression.
The results suggest that the investigation of CK20 mRNA with other biomarkers in the peripheral blood of breast cancer patients may be useful to monitor the presence of disseminated tumor cells in the blood circulation and to predict the prognosis of breast cancer.
乳腺癌患者的主要死因是转移。多种生物标志物已被用于早期检测乳腺癌患者外周血中的循环肿瘤细胞。本研究的目的是通过研究表皮生长因子受体(EGFR)、细胞角蛋白19(CK19)、细胞角蛋白20(CK20)和人表皮生长因子受体2(HER2)的表达谱来分析乳腺癌患者血液中的循环肿瘤细胞,并评估它们的预后重要性。
采用基于SYBR Green的实时定量聚合酶链反应(qPCR)检测法,对84例原发性浸润性导管癌女性患者和20名健康女性志愿者的血样进行CK19、CK20和EGFR基因表达谱评估。对46例HER2阳性原发性肿瘤患者和30名健康女性进行HER2表达分析,以确定阳性临界值。
外周血中CK20、EGFR、CK19和HER2 mRNA表达的阳性率分别为28.57%(24/84)、20.23%(17/84)、5.95%(5/84)和2.17%(1/46)。本研究首次发现乳腺癌患者外周血中CK20 mRNA表达的高阳性率。采用二元逻辑回归分析发现,CK20表达状态与几个与肿瘤侵袭性相关的临床参数存在显著差异。在有淋巴结转移和雌激素受体阴性的高级别原发性肿瘤患者中观察到较高的CK20阳性水平。我们已经证明CK20可能是一种新型生物标志物,有助于识别循环肿瘤细胞并预测乳腺癌进展。
结果表明,在乳腺癌患者外周血中联合其他生物标志物检测CK20 mRNA,可能有助于监测血液循环中播散肿瘤细胞的存在,并预测乳腺癌的预后。