Association Between Specific Mutations in KRAS Codon 12 and Colorectal Liver Metastasis.
Association Between Specific Mutations in KRAS Codon 12 and Colorectal Liver Metastasis.
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DOI：
10.1001/jamasurg.2015.0313
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发表时间：
2015-08
期刊：
影响因子：
16.9
通讯作者：
Pawlik TM
中科院分区：
文献类型：
--
作者：
Margonis GA;Kim Y;Spolverato G;Ejaz A;Gupta R;Cosgrove D;Anders R;Karagkounis G;Choti MA;Pawlik TM
目前，治疗结直肠肝转移（CRLM）患者最常用的生物标志物之一是Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）;然而，KRAS基因特定突变的预后意义仍未得到很好的定义。研究特定KRAS突变对因CRLM接受肝切除术患者的预后影响。本回顾性单中心研究于2003年1月1日至2013年12月31日进行。分析了2003年至2013年期间在约翰霍普金斯医院接受CRLM肝切除术的331例患者的特定KRAS突变数据。根据密码子12和13处的特定KRAS突变对临床病理特征、围手术期细节和结局进行分层。CRLM切除术。总生存期（OS）和无复发生存期。在91例患者（27.5%）中发现突变的KRAS（mtKRAS）。在中位随访27.4个月时，在48例mtKRAS患者（52.7%）和130例野生型KRAS（wtKRAS）患者（54.2%）中观察到复发（P = .82）。mtKRAS患者的中位和5年生存率分别为32.4个月和32.7%，wtKRAS患者分别为58.5个月和46.9%（P = 0.02）。与wtKRAS患者相比，KRAS密码子12突变患者的OS更差（风险比[HR]，1.54; 95%CI，1.05-2.27; P = .03），而KRAS密码子13突变与预后无关（HR，1.47; 95%CI，0.83-2.62; P = .19）。在密码子12和13的6种最常见的突变中，与wtKRAS患者相比，只有G12 V（HR，1.78; 95% CI，1.00-3.17; P = .05）和G12 S（HR，3.33; 95% CI，1.22-9.10; P = .02）与OS较差相关（均P < .05）。在复发的患者中，G12 V（HR，2.96; 95% CI，1.32-6.61; P = .01），G12 C（HR，6.74; 95% CI，2.05-22.2; P = .002）和G12 S突变（HR，4.91; 95% CI，1.52-15.8; P = .01）与OS较差相关（均P < .05）。CRLM切除术后复发的患者中，G12 V、G12 C和G12 S突变与OS恶化相关。关于特定KRAS突变的信息可能有助于CRLM切除患者的个体化治疗和监测策略。
Currently, one of the most commonly available biomarkers in the treatment of patients with colorectal liver metastases (CRLM) is the Kirsten rat sarcoma viral oncogene homolog (KRAS); however, the prognostic implications of specific mutations of the KRAS gene are still not well defined. To investigate the prognostic impact of specific KRAS mutations on patients undergoing liver resection for CRLM. This retrospective single-center study was conducted from January 1, 2003, to December 31, 2013. Data about specific KRAS mutations for 331 patients who underwent hepatic resection for CRLM at Johns Hopkins Hospital between 2003 and 2013 were analyzed. Clinicopathological characteristics, perioperative details, and outcomes were stratified by specific KRAS mutation at codons 12 and 13. Resection of CRLM. Overall survival (OS) and recurrence-free survival. A mutated KRAS (mtKRAS) was identified in 91 patients (27.5%). At a median follow-up of 27.4 months, recurrence was observed in 48 patients (52.7%) with mtKRAS and 130 patients (54.2%) with wild-type KRAS (wtKRAS) (P = .82). Median and 5-year survival among patients with mtKRAS was 32.4 months and 32.7%, respectively, vs 58.5 months and 46.9%, respectively, for patients with wtKRAS (P = .02). Patients with KRAS codon 12 mutations had worse OS (hazard ratio [HR], 1.54; 95% CI, 1.05–2.27; P = .03) vs those with wtKRAS, whereas a KRAS codon 13 mutation was not associated with prognosis (HR, 1.47; 95% CI, 0.83–2.62; P = .19). Among the 6 most common mutations in codons 12 and 13, only G12V (HR, 1.78; 95% CI, 1.00–3.17; P = .05) and G12S (HR, 3.33; 95% CI, 1.22–9.10; P = .02) were associated with worse OS compared with patients with wtKRAS (both P < .05). Among patients who recurred, G12V (HR, 2.96; 95% CI, 1.32–6.61; P = .01), G12C (HR, 6.74; 95% CI, 2.05–22.2; P = .002), and G12S mutations (HR, 4.91; 95% CI, 1.52–15.8; P = .01) were associated with worse OS (both P < .05). G12V and G12S mutations of codon 12 were independent prognostic factors of worse OS. Among patients who recurred after resection of CRLM, G12V, G12C, and G12S mutations were associated with worse OS. Information on specific KRAS mutations may help individualize therapeutic and surveillance strategies for patients with resected CRLM.