KRAS mutational status affects oxaliplatin-based chemotherapy independently from basal mRNA ERCC-1 expression in metastatic colorectal cancer patients
KRAS mutational status affects oxaliplatin-based chemotherapy independently from basal mRNA ERCC-1 expression in metastatic colorectal cancer patients
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DOI：
10.1038/bjc.2012.526
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发表时间：
2013-01-15
影响因子：
8.8
通讯作者：
Barone, C.
中科院分区：
文献类型：
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作者：
Basso, M.;Strippoli, A.;Barone, C.
背景：在本研究中，我们评估了 KRAS 突变状态可预测奥沙利铂 (OXA) 疗效的可能性。我们还探讨了切除修复交叉互补组1（ERCC-1）的作用。方法：对90例未接受过抗表皮生长因子受体治疗的晚期结直肠癌患者进行回顾性分析。对所有患者的 KRAS 突变状态进行了评估。还对 60 名患者的 mRNA ERCC-1 表达进行了研究。根据 KRAS 状态和 ERCC-1 mRNA 表达评估 FOLFOX-6 +/- 贝伐珠单抗治疗后的有效率 (RR) 和无进展生存期 (PFS)。 结果：在 90 名患者中，发现 47% 野生型 (wt) 和 53% 突变 (mt) KRAS 肿瘤。 wt KRAS 组的缓解率为 26%，而 mt KRAS 组的缓解率为 56%；在总样本中，差异具有统计学意义（P = 0.008），并且仅考虑接受 FOLFOX-6 +/- 贝伐珠单抗作为一线治疗的患者（P = 0.01）。所有患者（分别为 10 个月与 8 个月，P = 0.001）和一线治疗患者（分别为 10 个月与 8 个月，P = 0.0069）中，mt 患者的无进展生存期长于 wt KRAS 患者。 Mt KRAS 患者的生存期更长（24 个月 vs 18 个月；P = 0.01）。在我们的分析中，未发现 ERCC-1 mRNA 表达与 FOLFOX 活性相关。结论：我们的结果表明 KRAS 癌基因的激活突变可能预测对 OXA 的反应。 ERCC-1 mRNA 的基础表达并不能解释 FOLFOX-6 在 mt KRAS 患者中的高效作用。
Background: In this study, we evaluated the possibility that KRAS mutational status might be predictive of oxaliplatin (OXA) efficacy. We also explored the role of excision repair cross complementing group-1 (ERCC-1).Methods: Ninety anti-epidermal growth factor receptor-naive advanced colorectal cancer patients were retrospectively analysed. In all patients KRAS mutational status was assessed. In 60 patients mRNA ERCC-1 expression was also investigated. Response rate (RR) and progression-free survival (PFS) after FOLFOX-6 +/- bevacizumab were evaluated according to KRAS status and mRNA ERCC-1 expression.Results: Among 90 patients 47% wild-type (wt) and 53% mutated (mt) KRAS tumours were found. Response rate was 26% in the wt KRAS group, whereas it was 56% in the mt KRAS group; the difference is statistically significant in the total sample (P = 0.008) and when only patients receiving FOLFOX-6 +/- bevacizumab as first-line are considered (P = 0.01). Progression-free survival was longer in mt than in wt KRAS patients over all patients (10 vs 8 months, respectively, P = 0.001) and in those treated as first-line (10 vs 8 months, respectively, P = 0.0069). Mt KRAS patients experienced a longer survival (24 vs 18 months; P = 0.01). ERCC-1 mRNA expression was not found to correlate with FOLFOX activity in our analysis.Conclusion: Our results suggest that activating mutation of KRAS oncogene may predict response to OXA. Basal expression of ERCC-1 mRNA does not explain the high efficacy of FOLFOX-6 in mt KRAS patients.