Zocche David M, Ramirez Carolina, Fontao Fernando M, Costa Lucas D, Redal María A
Molecular and Cellular Biology Department, Instituto Universitario del Hospital Italiano de Buenos Aires - Hospital Italiano de Buenos Aires, Buenos Aires Argentina.
Instituto de Ciencias Básicas y Medicina Experimental, Instituto Universitario del Hospital Italiano de Buenos Aires - Hospital Italiano de Buenos Aires, Buenos Aires Argentina.
Front Genet. 2015 Mar 30;6:116. doi: 10.3389/fgene.2015.00116. eCollection 2015.
Colorectal cancer (CRC) is one of the most frequent events in oncology. Advances in molecular understanding of the processes of carcinogenesis have shed light on the fundamental mechanisms of tumorigenesis. Currently, knowledge of the molecular basis of its pathogenesis is being used to improve patient care and devise more rational therapeutics. Still, the role played by the mutation patterns of mutated genes in the clinical outcomes that patients on pharmacological treatment receive remains unclear. In this study, we propose to analyze the different clinical outcomes and disease prognosis of patients with stage IV CRC treated with FOLFOX chemotherapy (fluorouracil, leucovorin, oxaliplatin) based on different Kirsten ras (KRAS) mutation patterns.
In this cohort study, 148 patients diagnosed with stage IV CRC and treated with FOLFOX were studied between 2008 and 2013. Mutational status of KRAS was determined. Progression-free survival (PFS) and overall survival (OS) were measured, and all deaths were verified. Survival analysis was performed using Kaplan-Meier analysis, comparison among groups was analyzed using the log-rank test, and multivariate analysis was conducted using Cox proportional-hazards regression.
Among a total of 148 patients, 48 (32%) had mutated KRAS, 77% at codon 12 and 23% at codon 13. The PFS was significantly worse in the mutant KRAS patients in comparison to wild type KRAS patients (p < 0.05). The OS did not show significant differences between the two groups. Multivariate analysis showed KRAS mutation as an independent negative prognostic factor for PFS. Among the various subtypes of KRAS mutation, G12D was significantly associated with a poor prognosis in PFS (p = 0.02).
In our population, the KRAS mutation had an adverse impact on the prognosis for stage IV CRC patients treated with the FOLFOX regimen.
结直肠癌（CRC）是肿瘤学中最常见的病症之一。对致癌过程分子理解的进展揭示了肿瘤发生的基本机制。目前，其发病机制的分子基础知识正被用于改善患者护理并设计更合理的治疗方法。然而，突变基因的突变模式在接受药物治疗的患者临床结局中所起的作用仍不清楚。在本研究中，我们建议基于不同的 Kirsten 大鼠肉瘤病毒癌基因（KRAS）突变模式，分析接受 FOLFOX 化疗（氟尿嘧啶、亚叶酸钙、奥沙利铂）治疗的IV期CRC患者的不同临床结局和疾病预后。
在这项队列研究中，对2008年至2013年间诊断为IV期CRC并接受FOLFOX治疗的148例患者进行了研究。确定了KRAS的突变状态。测量了无进展生存期（PFS）和总生存期（OS），并对所有死亡病例进行了核实。使用Kaplan-Meier分析进行生存分析，使用对数秩检验分析组间比较，并使用Cox比例风险回归进行多变量分析。
在总共148例患者中，48例（32%）KRAS发生突变，12密码子处突变占77%，13密码子处突变占23%。与野生型KRAS患者相比，突变型KRAS患者的PFS明显更差（p < 0.05）。两组之间的OS没有显著差异。多变量分析显示KRAS突变是PFS的独立负面预后因素。在KRAS突变的各种亚型中，G12D与PFS预后不良显著相关（p = 0.02）。
在我们的研究人群中，KRAS突变对接受FOLFOX方案治疗的IV期CRC患者的预后有不利影响。
