KRAS mutations by digital PCR in circulating tumor cells isolated from the mesenteric vein are associated with residual disease and overall survival in resected colorectal cancer patients.
Int J Colorectal Dis
; 35(5): 805-813, 2020 May.
Article
em En
| MEDLINE
| ID: mdl-32088737
ABSTRACT
PURPOSE:
In colorectal cancer (CRC), circulating tumor cells (CTCs) are released into the mesenteric veins (MV). We chose to determine whether KRAS mutations detected in CTCs from blood obtained at the time of surgery could be a marker of survival.METHODS:
From 52 surgically resected CRC patients who later relapsed, samples of tumor tissue, normal tissue, and blood from the peripheral vein (PV) and MV were obtained from each patient at the time of surgery. KRAS mutations were assessed by Sanger sequencing and digital PCR (DGPCR) in tissue samples and by DGPCR in CTCs. Mutant KRAS copy number was assessed in CTCs. Results were correlated with overall survival (OS).RESULTS:
Sanger sequencing detected KRAS mutations in ten tumor samples (19.2%), while DGPCR detected mutations in 30 (58%). Mutations were detected in CTCs in 21 MV samples (40.4%) and 18 PV samples (34.6%). Patients with G13D mutations in CTCs from the MV had shorter OS than those with G12D mutations (28.1 vs 54.6 months; p = 0.025). Patients with a high mutant KRAS copy number in CTCs had shorter OS than those with a low mutant KRAS copy number (MV 20.5 vs 43.7 months; p = 0.002; PV 15.1 vs 38.2 months; p = 0.027).CONCLUSION:
DGPCR is more efficient than Sanger sequencing for detecting KRAS mutations. KRAS G13D mutations and high mutant KRAS copy number are associated with shorter OS. The analysis of KRAS mutations in CTCs from blood obtained at the time of surgery can identify patients with a higher risk of relapse.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Reação em Cadeia da Polimerase
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Proteínas Proto-Oncogênicas p21(ras)
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Neoplasia Residual
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Veias Mesentéricas
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Mutação
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Células Neoplásicas Circulantes
Tipo de estudo:
Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Int J Colorectal Dis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Espanha