State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital & Institute, Beijing, China.
Cancer Med. 2024 Oct;13(19):e70168. doi: 10.1002/cam4.70168.
The prognostic and predictive value of RAS mutations in patients with colorectal liver metastases (CRLM) who have undergone hepatectomy holds substantial importance. The present study aimed to investigate the impact of different RAS codon mutations on long-term survival in CRLM patients.
A retrospective analysis was conducted on clinicopathological data from 399 CRLM patients with RAS mutations who underwent hepatectomy between January 2000 and December 2020. The RAS mutation gene status was assessed in KRAS codons (G12, G13, Q61, and A146) and NRAS codons (G12, G13, and Q61). Survival curves were generated using the Kaplan-Meier plotter and compared using the log-rank test. Univariate and multivariate analyses were performed to analyze the clinicopathological data.
In the entire cohort, patients with KRAS G12 mutations exhibited the most favorable prognosis (p = 0.018). Comparatively, patients harboring KRAS Q61 mutations experienced poorer overall survival (OS) with a median of 15 months versus 33 months (p = 0.011) when compared to those with KRAS G12 mutations. Moreover, patients with NRAS Q61 mutations also showed decreased OS with a median of 26 months versus 33 months (p = 0.020) in comparison to KRAS G12 mutation patients. The results of multivariate analysis showed that both KRAS Q61 mutation (HR 2.130; 95% CI 1.088-4.168; p = 0.027) and NRAS Q61 mutation (HR 2.877; 95% CI 1.398-5.922; p = 0.004) were independent influencing factors of OS. Based on all identified risk factors, patients with RAS mutation were divided into high-risk and low-risk groups. Notably, in the high-risk group, the incorporation of postoperative chemotherapy was associated with longer OS, while it did not improve the survival of patients in the low-risk group.
KRAS Q61 and NRAS Q61 mutations are promising predictors for OS in CRLM patients after hepatectomy. Postoperative chemotherapy may significantly benefit CRLM patients with RAS mutations, particularly those identified as high-risk.
在接受肝切除术的结直肠癌肝转移（CRLM）患者中，RAS 突变的预后和预测价值具有重要意义。本研究旨在探讨不同 RAS 密码子突变对 CRLM 患者长期生存的影响。
回顾性分析了 2000 年 1 月至 2020 年 12 月期间接受肝切除术的 399 例 RAS 突变的 CRLM 患者的临床病理资料。评估 KRAS 密码子（G12、G13、Q61 和 A146）和 NRAS 密码子（G12、G13 和 Q61）中的 RAS 突变基因状态。使用 Kaplan-Meier 绘图仪生成生存曲线，并使用对数秩检验进行比较。对临床病理数据进行单因素和多因素分析。
在整个队列中，KRAS G12 突变患者的预后最佳（p=0.018）。相比之下，携带 KRAS Q61 突变的患者总生存期（OS）较差，中位 OS 为 15 个月，而 KRAS G12 突变患者为 33 个月（p=0.011）。此外，与 KRAS G12 突变患者相比，携带 NRAS Q61 突变的患者 OS 也降低，中位 OS 为 26 个月，而 KRAS G12 突变患者为 33 个月（p=0.020）。多因素分析结果显示，KRAS Q61 突变（HR 2.130；95%CI 1.088-4.168；p=0.027）和 NRAS Q61 突变（HR 2.877；95%CI 1.398-5.922；p=0.004）均是 OS 的独立影响因素。基于所有确定的危险因素，将 RAS 突变患者分为高危组和低危组。值得注意的是，在高危组中，术后化疗与更长的 OS 相关，而在低危组中，化疗并未改善患者的生存。
KRAS Q61 和 NRAS Q61 突变是结直肠癌肝转移患者肝切除术后 OS 的有前途的预测因子。术后化疗可能显著获益于 RAS 突变的 CRLM 患者，尤其是高危患者。
