Prognostic significance of CEACAM5 mRNA-positive circulating tumor cells in patients with metastatic colorectal cancer

Abstract

Purpose

Τo evaluate the clinical relevance of CEACAM5mRNA-positive circulating tumor cells (CTCs) in patients with metastatic colorectal cancer (mCRC).

Methods

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.

Results

The patients' median age was 67 years and PS (EGOG 0–1) 92%; KRAS exon 2 and BRAF^V600E 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^V600E 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).

Conclusions

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.

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