Lu Weipeng, Wei Hong, Li Mei, Wang Hai, Liu Lina, Zhang Qiuping, Liu Lisha, Lu Shen
Laboratory Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116000, P.R. China.
Department of Pathology, The Third People's Hospital of Dalian, Dalian, Liaoning 116000, P.R. China.
Mol Med Rep. 2015 Jul;12(1):1219-24. doi: 10.3892/mmr.2015.3530. Epub 2015 Mar 23.
Cetuximab, an immunoglobulin G1 chimeric monoclonal antibody directed against the epidermal growth factor receptor, is currently considered to be the strategy with the most potential for the treatment of gastric cancer due to the low frequency of KRAS mutations in patients with gastric cancer. However, the therapeutic success of cetuximab in colorectal cancer (CRC) has demonstrated that the clinical effect of cetuximab is closely dependent not only on KRAS mutations, but also BRAF and phosphoinositide-3-kinase, catalytic, α polypeptide (PIK3CA) mutations. In the present study, the status of KRAS, BRAF and PIK3CA mutations in gastric cancer were investigated concomitantly in order to aid the selection of patients eligible for treatment with cetuximab. Mutations in KRAS (exon 2), BRAF (exon 15) and PIK3CA (exon 9 and exon 20) were retrospectively evaluated by high resolution melting analysis and DNA direct sequencing in samples from 156 patients with gastric cancer. Mutations in either KRAS or PIK3CA were identified in 13 samples (8.3%), 7 samples with KRAS mutations and 6 samples with PIK3CA mutations. No mutations in the BRAF gene were identified. The frequency of mutations in either KRAS or PIK3CA were significantly higher in patients without lymph node metastasis than those with. Furthermore, KRAS and PIK3CA mutations were mutually exclusive. The present study, therefore, suggested that it may be necessary to evaluate KRAS and PIK3CA mutations concomitantly for the selection of patients eligible for treatment with cetuximab.
西妥昔单抗是一种针对表皮生长因子受体的免疫球蛋白G1嵌合单克隆抗体，由于胃癌患者中KRAS突变频率较低，目前被认为是治疗胃癌最具潜力的策略。然而，西妥昔单抗在结直肠癌（CRC）中的治疗成功表明，西妥昔单抗的临床效果不仅密切依赖于KRAS突变，还与BRAF和磷脂酰肌醇-3-激酶催化亚基α多肽（PIK3CA）突变有关。在本研究中，同时调查了胃癌中KRAS、BRAF和PIK3CA突变的情况，以帮助选择适合接受西妥昔单抗治疗的患者。通过高分辨率熔解分析和DNA直接测序，对156例胃癌患者样本中的KRAS（第2外显子）、BRAF（第15外显子）和PIK3CA（第9和第20外显子）突变进行了回顾性评估。在13个样本（8.3%）中鉴定出KRAS或PIK3CA突变，7个样本为KRAS突变，6个样本为PIK3CA突变。未鉴定出BRAF基因的突变。无淋巴结转移患者中KRAS或PIK3CA突变的频率显著高于有淋巴结转移的患者。此外，KRAS和PIK3CA突变相互排斥。因此，本研究表明，为了选择适合接受西妥昔单抗治疗的患者，可能有必要同时评估KRAS和PIK3CA突变。
