Clinicopathological features and prognostic roles of KRAS, BRAF, PIK3CA and NRAS mutations in advanced gastric cancer

被引：41
作者：
Takahashi N. [1 ]
Yamada Y. [1 ]
Taniguchi H. [2 ]
Fukahori M. [1 ]
Sasaki Y. [1 ]
Shoji H. [1 ]
Honma Y. [1 ]
Iwasa S. [1 ]
Takashima A. [1 ]
Kato K. [1 ]
Hamaguchi T. [1 ]
Shimada Y. [1 ]
机构：
[1] Gastrointestinal Oncology Division, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045
[2] Division of Pathology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045
来源：
BMC Research Notes | / 7卷 / 1期
关键词：
Overall Survival; Advanced Gastric Cancer; KRAS Mutation; PIK3CA Mutation; Molecular Target Therapy;
D O I：
10.1186/1756-0500-7-271
中图分类号：
学科分类号：
摘要：
Background: RAS-RAF-MEK-ERK and PI3K-AKT pathways form a significant cascade for potential molecular target therapy in advanced cancer. The clinical significance of mutations in these genes in advanced gastric cancer (AGC) is uncertain. Methods. We collected formalin-fixed, paraffin-embedded and fresh frozen tumor samples from AGC patients and analyzed the KRAS, NRAS, BRAF and PIK3CA mutations by direct-sequencing. We retrospectively investigated the clinicopathological features of these mutations in AGC patients, and selected patients with metastatic gastric cancer. Results: Among 167 AGC patients, mutations of KRAS codons 12/13 (N = 8/164, 4.9%), PIK3CA (N = 9/163, 5.5%), and NRAS codon 12/13(N = 3/159, 1.9%) were detected. Comparison of the clinicopathological features of the mutated KRAS, PIK3CA, NRAS genes with an all-wild type of these genes showed that the frequency of the intestinal type was significantly higher in patients whose tumor tissue contained KRAS mutations (P = 0.014). Among 125 patients with metastatic gastric cancer, patients with NRAS codon 12/13 mutations in their tumors had shorter overall survival compared with NRAS wild-type patients (MST: 14.7 vs 8.8 months, P = 0.011). By multivariate analyses, NRAS codon 12/13 mutation was an indicator for poor prognosis in patients with metastatic gastric cancer (adjusted HR 5.607, 95% CI: 1.637-19.203). Conclusions: Our study indicated that mutations of KRAS, PIK3CA and NRAS were rare in AGC. NRAS mutations were likely to associate with poor prognosis in metastatic state of AGC patients, but further validation of other research is required. © 2014 Takahashi et al.; licensee BioMed Central Ltd.
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