Research Center for Clinical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu Province, China.
PLoS One. 2013 Jul 9;8(7):e68022. doi: 10.1371/journal.pone.0068022. Print 2013.
Epidermal growth factor receptor monoclonal antibody was approved for treatment of metastatic colorectal cancer patients carrying KRAS wild type DNA. However, recent studies showed that patients with KRAS G13D mutation may benefit from EGFR antibody therapy. In this study we tried to explore whether the abundance of KRAS mutation could affect the efficacy of EGFR antibody therapy. We firstly established a PNA-PCR method which could calculate the percentage of KRAS mutation in total DNA and proved its ability on 47 colorectal cancer samples bearing KRAS mutations. Then we analyzed the correlation between the abundance of KRAS mutations and efficacy of EGFR antibody therapy in another 35 metastatic colorectal cancer patients. We proved that PNA-PCR assay could calculate the abundance of KRAS mutation and the percentage of mutant DNA in tumor cells varied a lot (10.8%∼98.3%) on the 47 colorectal cancer patients. The efficacy of EGFR antibody correlated with the abundance of KRAS mutations: in the KRAS mutation less than 30% group, the disease control rate was 44.4% (4/9); the disease control rate of 30∼80% group was 5.6% (1/18) and the >80% group was 12.5% (1/8) (P = 0.038). In summary, our study showed that PNA-PCR method could easily detect the percentage of KRAS mutation in tumor cells and colorectal cancer patients with low abundance of KRAS mutation might benefit from EGFR antibody therapy.
表皮生长因子受体单克隆抗体被批准用于治疗携带 KRAS 野生型 DNA 的转移性结直肠癌患者。然而，最近的研究表明，携带 KRAS G13D 突变的患者可能受益于 EGFR 抗体治疗。在这项研究中，我们试图探讨 KRAS 突变的丰度是否会影响 EGFR 抗体治疗的疗效。我们首先建立了一种 PNA-PCR 方法，该方法可以计算总 DNA 中 KRAS 突变的百分比，并在 47 例携带 KRAS 突变的结直肠癌样本中证明了其能力。然后，我们分析了 35 例转移性结直肠癌患者中 KRAS 突变丰度与 EGFR 抗体治疗疗效之间的相关性。我们证明 PNA-PCR 测定法可以计算 KRAS 突变的丰度，并且肿瘤细胞中突变 DNA 的百分比差异很大（10.8%∼98.3%）。在 47 例结直肠癌患者中，EGFR 抗体的疗效与 KRAS 突变的丰度相关：在 KRAS 突变<30%的组中，疾病控制率为 44.4%（4/9）；在 30%∼80%的组中，疾病控制率为 5.6%（1/18），而>80%的组为 12.5%（1/8）（P = 0.038）。综上所述，我们的研究表明，PNA-PCR 方法可以轻松检测肿瘤细胞中 KRAS 突变的百分比，并且 KRAS 突变丰度低的结直肠癌患者可能受益于 EGFR 抗体治疗。
