Ogura Toshiro, Kakuta Miho, Yatsuoka Toshimasa, Nishimura Yoji, Sakamoto Hirohiko, Yamaguchi Kensei, Tanabe Minoru, Tanaka Yoichi, Akagi Kiwamu
Division of Gastroenterological Surgery, Saitama Cancer Center, Saitama 362-0806, Japan.
Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama 362-0806, Japan.
Oncol Rep. 2014 Jul;32(1):50-6. doi: 10.3892/or.2014.3165. Epub 2014 May 6.
At present, molecular markers of colorectal cancer (CRC), including KRAS, NRAS and BRAF mutations, and the microsatellite status are evaluated for the development of personalized treatments. However, clinicopathological and molecular characteristics and the prognostic role of NRAS mutations remain unclear. In the present study, a total of 1,304 consecutive stage 0-IV CRC tumor samples were analyzed for KRAS (exon 2, 3 and 4), NRAS (exon 2 and 3) and BRAF (exon 15) mutations. Multivariate analysis was performed to assess the prognostic impact of NRAS mutations. KRAS, NRAS and BRAF mutations were identified in 553 (42.4%), 35 (2.7%), and 59 (4.5%) of 1,304 CRC cases, respectively. Tumors with NRAS mutations were more frequently located in the distal colorectum compared with those with KRAS or BRAF mutations. Multivariate analysis indicated that KRAS and BRAF mutations were found to be associated with poor prognosis [hazard ratio (HR)=1.44, 95% confidence interval (CI), 1.18-1.76 and HR=2.09; 95% CI, 1.33-3.28, respectively], whereas NRAS mutations were associated with a trend toward favorable prognosis (HR=0.53; 95% CI, 0.27-1.03). Characteristics and prognosis of CRC with NRAS mutations are different from those with KRAS or BRAF mutations.
目前，针对结直肠癌（CRC）的分子标志物，包括KRAS、NRAS和BRAF突变以及微卫星状态，进行评估以制定个性化治疗方案。然而，NRAS突变的临床病理和分子特征及其预后作用仍不明确。在本研究中，对总共1304例连续的0-IV期CRC肿瘤样本进行了KRAS（第2、3和4外显子）、NRAS（第2和3外显子）和BRAF（第15外显子）突变分析。进行多变量分析以评估NRAS突变的预后影响。在1304例CRC病例中，分别有553例（42.4%）、35例（2.7%）和59例（4.5%）检测到KRAS、NRAS和BRAF突变。与KRAS或BRAF突变的肿瘤相比，NRAS突变的肿瘤更常位于结直肠远端。多变量分析表明，KRAS和BRAF突变与预后不良相关[风险比（HR）=1.44，95%置信区间（CI），1.18-1.76和HR=2.09；95%CI，1.33-3.28]，而NRAS突变与预后良好的趋势相关（HR=0.53；95%CI，0.27-1.03）。NRAS突变的CRC的特征和预后与KRAS或BRAF突变的CRC不同。
