Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Stavrakia and Voutes, 71100, Heraklion, Crete, Greece.
Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Crete, Greece.
Cancer Chemother Pharmacol. 2018 Nov;82(5):767-775. doi: 10.1007/s00280-018-3666-9. Epub 2018 Aug 9.
Τo evaluate the clinical relevance of CEACAM5mRNA-positive circulating tumor cells (CTCs) in patients with metastatic colorectal cancer (mCRC).
Peripheral blood was obtained from 436 patients with mCRC before the initiation of systemic therapy. A second sample was obtained on treatment assessment from 296 (67.9%) patients. The detection of CEACAM5mRNA-positive CTCs was performed using a real-time PCR assay.
The patients' median age was 67 years and PS (EGOG 0-1) 92%; KRAS exon 2 and BRAF mutated primary tumors were identified in 31.9% and 6.4% of the tested patients, respectively, whereas metastasectomy was performed in 17.7% of the patients. Circulating CEACAM5mRNA-positive CTCs were detected in 125 (28.7%) and 85 (28.7%) patients at baseline and on treatment assessment, respectively. The detection of CEACAM5mRNA-positive cells was revealed, in multivariate analysis, as an independent prognostic factor associated with decreased PFS (HR 1.6; 95% CI 1.1-2.5; p = 0.026) and OS (HR 2.2; 95% CI 1.3-3.2; p < 0.001). The detection of CEACAM5mRNA-positive CTCs in patients with KRAS and BRAF mutations was correlated with shorter PFS (p = 0.041 and p = 0.022, respectively). Moreover, OS was significantly shorter in patients with CEACAM5+/KRAS mutations compared to those with CEACAM5+/KRAS wt tumors (p = 0.023).
Detection of peripheral blood CEACAM5mRNA-positive CTCs is an adverse prognostic factor correlated with poor clinical outcome in patients with mCRC, especially in patients with KRAS and BRAF mutated tumors.
评估转移性结直肠癌(mCRC)患者中 CEACAM5mRNA 阳性循环肿瘤细胞(CTC)的临床相关性。
在开始系统治疗前,采集 436 名 mCRC 患者的外周血。对 296 名(67.9%)患者的治疗评估中获得了第二份样本。使用实时 PCR 检测法检测 CEACAM5mRNA 阳性 CTC。
患者的中位年龄为 67 岁,PS(ECOG 0-1)为 92%;在检测的患者中,31.9%和 6.4%的患者存在 KRAS 外显子 2 和 BRAF 突变的原发肿瘤,17.7%的患者进行了转移灶切除术。基线和治疗评估时分别有 125(28.7%)和 85(28.7%)名患者检测到循环 CEACAM5mRNA 阳性 CTC。在多变量分析中,CEACAM5mRNA 阳性细胞的检测被揭示为与 PFS(HR 1.6;95%CI 1.1-2.5;p=0.026)和 OS(HR 2.2;95%CI 1.3-3.2;p<0.001)缩短相关的独立预后因素。在 KRAS 和 BRAF 突变的患者中检测到 CEACAM5mRNA 阳性 CTC 与较短的 PFS 相关(p=0.041 和 p=0.022)。此外,CEACAM5+/KRAS 突变患者的 OS 明显短于 CEACAM5+/KRAS wt 肿瘤患者(p=0.023)。
外周血 CEACAM5mRNA 阳性 CTC 的检测是 mCRC 患者不良预后因素,与临床结局较差相关,特别是在 KRAS 和 BRAF 突变的肿瘤患者中。