阐明KRAS、NRAS、BRAF和PIK3CA突变在中国转移性结直肠癌患者中的预后意义。

Elucidating the prognostic significance of KRAS, NRAS, BRAF and PIK3CA mutations in Chinese patients with metastatic colorectal cancer.

作者信息

Ma Brigette B, Mo Frankie, Tong Joanna H, Wong Ashley, Wong S C Cesar, Ho Wing M, Wu Cherry, Lam Polly W Y, Chan K F, Chan Timothy S K, Tsui Wilson M S, Tsang Alex K H, Fung Mandy N S, Chan Anthony T C, To Ka Fai

机构信息

State Key Laboratory in Oncology in South China, Sir YK Pao Centre for Cancer, Department of Clinical Oncology, Hong Kong Cancer Institute and the Chinese University of Hong Kong, Hong Kong.

出版信息

Asia Pac J Clin Oncol. 2015 Jun;11(2):160-9. doi: 10.1111/ajco.12342. Epub 2015 Apr 13.

DOI:10.1111/ajco.12342

PMID:25865669

Abstract

AIM

The prognostic significance of KRAS, NRAS, PIK3CA and BRAF mutations was evaluated in Chinese patients with metastatic colorectal cancer (CRC).

METHOD

Tumor samples from 183 patients were retrospectively tested for KRAS, NRAS, PIK3CA and BRAF mutations. Multivariate analysis was performed to determine the relationship between mutational status, drug response and survival.

RESULT

Over 70% of patients received two or more lines of chemotherapy, 50% had cetuximab and 18% had bevacizumab. The prevalence of KRAS, NRAS, BRAF and PIK3CA mutations was 45, 3.2, 5 and 20%, respectively. For the entire cohort, the median overall survival was 24 months (95% confidence interval [CI] = 20.4-26.4 months). Of the genes tested, only KRAS mutation was an independent prognostic factor with a multivariate hazard ratio of 1.5 (95% CI = 1.05-2.16, P = 0.03). In the subgroup of patients who received cetuximab-based therapy in the first-line setting, KRAS mutation was associated with a lack of response to chemotherapy (28% vs 66%, chi-square, P = 0.01). Patients with KRAS mutant tumors (or KRAS wild-type tumors that harbored BRAF and/or PIK3CA mutations) tended to have lower response rates to chemotherapy and/or cetuximab (P = not significant). The number of NRAS mutant cases was too small to allow any statistical analysis.

CONCLUSION

The prevalence of KRAS, NRAS, BRAF and PIK3CA mutations in this cohort is consistent with reports from non-Asian populations, and KRAS mutation has both prognostic and predictive significance in Chinese patients with metastatic CRC.

摘要

目的

评估KRAS、NRAS、PIK3CA和BRAF基因突变在中国转移性结直肠癌（CRC）患者中的预后意义。

方法

回顾性检测183例患者的肿瘤样本中的KRAS、NRAS、PIK3CA和BRAF基因突变。进行多因素分析以确定突变状态、药物反应和生存之间的关系。

结果

超过70%的患者接受了两线或更多线化疗，50%接受了西妥昔单抗治疗，18%接受了贝伐单抗治疗。KRAS、NRAS、BRAF和PIK3CA基因突变的发生率分别为45%、3.2%、5%和20%。对于整个队列，中位总生存期为24个月（95%置信区间[CI]=20.4 - 26.4个月）。在所检测的基因中，只有KRAS突变是独立的预后因素，多因素风险比为1.5（95%CI = 1.05 - 2.16，P = 0.03）。在一线接受基于西妥昔单抗治疗的患者亚组中，KRAS突变与化疗无反应相关（28%对66%，卡方检验，P = 0.01）。KRAS突变肿瘤患者（或携带BRAF和/或PIK3CA突变的KRAS野生型肿瘤患者）对化疗和/或西妥昔单抗的反应率往往较低（P = 无显著性差异）。NRAS突变病例数太少，无法进行任何统计分析。