Τίτλος:
Prognostic significance of CEACAM5mRNA-positive circulating tumor cells in patients with metastatic colorectal cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 BRAFV600E 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 BRAFV600E 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. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
Συγγραφείς:
Messaritakis, I.
Sfakianaki, M.
Papadaki, C.
Koulouridi, A.
Vardakis, N.
Koinis, F.
Hatzidaki, D.
Georgoulia, N.
Kladi, A.
Kotsakis, A.
Souglakos, J.
Georgoulias, V.
Περιοδικό:
Cancer Chemotherapy and Pharmacology
Λέξεις-κλειδιά:
B Raf kinase; K ras protein; messenger RNA; messenger RNA ceacam5; unclassified drug; carcinoembryonic antigen; CEACAM5 protein, human; glycosylphosphatidylinositol anchored protein; messenger RNA, adult; aged; Article; blood sampling; cancer patient; cancer prognosis; cancer surgery; circulating tumor cell; clinical evaluation; exon; female; human; major clinical study; male; metastasis resection; metastatic colorectal cancer; primary tumor; priority journal; prospective study; real time polymerase chain reaction; systemic therapy; blood; cancer staging; colorectal tumor; genetics; Kaplan Meier method; metabolism; metastasis; mononuclear cell; pathology; predictive value; tumor embolism, Aged; Carcinoembryonic Antigen; Colorectal Neoplasms; Female; GPI-Linked Proteins; Humans; Kaplan-Meier Estimate; Leukocytes, Mononuclear; Male; Neoplasm Metastasis; Neoplasm Staging; Neoplastic Cells, Circulating; Predictive Value of Tests; Progression-Free Survival; Prospective Studies; RNA, Messenger
DOI:
10.1007/s00280-018-3666-9
