Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, 650-0047, Japan.
Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, 755-0046, Japan.
BMC Cancer. 2021 May 7;21(1):518. doi: 10.1186/s12885-021-08271-z.
RAS/BRAF mutations are the most remarkable oncogenic driver mutations in colorectal cancer (CRC) and play an important role in treatment selection. No data are available regarding the clinical and prognostic features of patients with detailed RAS/BRAF-mutant metastatic CRC (mCRC) in Japan.
A total of 152 chemotherapy-naïve patients with mCRC were included in this study between August 2018 and July 2019. Tumor samples were collected, and RAS/BRAF status was investigated. RAS/BRAF status was examined using a MEBGEN RASKET-B kit and polymerase chain reaction reverse sequence-specific oligonucleotide method.
RAS/BRAF mutations were detected in 54% of cases (KRAS codon 12, 26%; KRAS codon 13, 17%; KRAS non-Exon2, 5%; NRAS, 5%; and BRAF, 7%). BRAF-mutant CRC mainly existed in the right colon, whereas KRAS non-Exon2 and NRAS-mutant CRC was predominantly present in the left colon. KRAS non-Exon2 and NRAS-mutant CRC were associated with shorter survival time than RAS wild-type CRC (hazard ratio [HR], 2.26; 95% confidence interval [CI], 0.64-8.03; p = 0.19; HR, 2.42; 95% CI, 0.68-8.61; p = 0.16) and significantly shorter overall survival than KRAS Exon2-mutant CRC (HR, 3.88; 95% CI, 0.92-16.3; p = 0.04; HR, 4.80; 95% CI, 1.14-20.2; p = 0.02).
In our multicenter study, the findings elucidated the clinical and prognostic features of patients with detailed RAS/BRAF-mutant mCRC in Japan.
RAS/BRAF 突变是结直肠癌(CRC)中最显著的致癌驱动突变,在治疗选择中发挥重要作用。在日本,尚无关于详细的 RAS/BRAF 突变转移性 CRC(mCRC)患者的临床和预后特征的数据。
本研究共纳入 2018 年 8 月至 2019 年 7 月期间 152 例化疗初治 mCRC 患者。采集肿瘤样本并检测 RAS/BRAF 状态。采用 MEBGEN RASKET-B 试剂盒和聚合酶链反应反向序列特异性寡核苷酸方法检测 RAS/BRAF 状态。
在 54%的病例中检测到 RAS/BRAF 突变(KRAS 密码子 12,17%;KRAS 密码子 13,17%;KRAS 非外显子 2,5%;NRAS,5%;BRAF,7%)。BRAF 突变型 CRC 主要存在于右半结肠,而 KRAS 非外显子 2 和 NRAS 突变型 CRC 主要存在于左半结肠。KRAS 非外显子 2 和 NRAS 突变型 CRC 与 RAS 野生型 CRC 相比生存时间更短(风险比 [HR],2.26;95%置信区间 [CI],0.64-8.03;p=0.19;HR,2.42;95%CI,0.68-8.61;p=0.16),与 KRAS 外显子 2 突变型 CRC 相比总生存期明显更短(HR,3.88;95%CI,0.92-16.3;p=0.04;HR,4.80;95%CI,1.14-20.2;p=0.02)。
在我们的多中心研究中,研究结果阐明了日本详细的 RAS/BRAF 突变 mCRC 患者的临床和预后特征。