Association of KRAS Variant Subtypes With Survival and Recurrence in Patients With Surgically Treated Intrahepatic Cholangiocarcinoma.
Association of KRAS Variant Subtypes With Survival and Recurrence in Patients With Surgically Treated Intrahepatic Cholangiocarcinoma.
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KRAS 变异亚型与手术治疗的肝内胆管癌患者的生存和复发的关系。
DOI：
10.1001/jamasurg.2021.5679
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发表时间：
2022-01-01
期刊：
影响因子：
16.9
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Zhou SL;Xin HY;Sun RQ;Zhou ZJ;Hu ZQ;Luo CB;Wang PC;Li J;Fan J;Zhou J
在手术治疗的肝内胆管癌（ICC）患者中，KRAS变异亚型的患病率及其与生存和复发的关系是什么？在这项包括1024例患者的队列研究中，共鉴定出影响127例ICC患者（12.4%）的14种不同KRAS体细胞变异亚型，包括G12D（43.3%）、G12V（19.7%）、G12C（7.1%）和G13D（6.3%）。G12 KRAS变异而非非G12 KRAS变异与较差的总生存期和无病生存期独立相关，G12V KRAS变异是最差的总生存期和无病生存期最强的预后决定因素。这项队列研究在一个大型ICC患者队列中确定了KRAS变异亚型的分布，并显示了与患者预后的关联。本队列研究探讨了KRAS变异亚型与肝内胆管癌患者生存和复发的预后关系。KRAS变异与肿瘤进展相关；然而，KRAS变异亚型的患病率及其与肝内胆管癌（ICC）根治性切除后患者的生存和复发的关系在很大程度上是未知的。探讨KRAS变异亚型与ICC患者生存和复发的预后关系。在这项队列研究中，招募了2009年1月至2016年12月在中国一家医院接受根治性ICC切除术的患者，并进行了全外显子组测序、靶向测序和Sanger测序以鉴定KRAS变异体。Kaplan-Meier和log-rank检验用于比较总生存期（OS）和无病生存期（DFS）。采用Cox比例风险回归模型进行单因素和多因素分析。数据分析时间为2020年4月至2021年1月。ICC患者的肝切除术。KRAS变异亚型与OS和DFS的关系。在纳入的1024例ICC患者中，621例（60.6%）为男性，平均（SD）年龄为59.2（10.2）岁。共鉴定出14种不同的KRAS体细胞变异亚型，影响127例患者（12.4%）。G12D是该队列中最常见的等位基因，在鉴定的127个KRAS变异中占55个（43.3%），其次是G12V（25个[19.7%]）、G12C（9个[7.1%]）和G13D（8个[6.3%]）。与野生型KRAS患者相比，变异KRAS患者更容易出现高水平的碳水化合物抗原19-9(127例中有92例[72.4%]vs 897例中有546例[60.9%];P =。γ-谷氨酰转移酶（72 / 127 [56.7%]vs 420 / 897 [46.8%]; P = .04）。多变量分析显示，G12 KRAS变异而非G12 KRAS变异与较差的OS独立相关(风险比[HR]， 1.69; 95% CI, 1.31-2.18; P <。001)和DFS (HR 1.47; 95%可信区间,1.16 - -1.88;P = .002)。在G12 KRAS变异患者中，G12V KRAS变异是最坏OS的最强预后决定因素（HR, 3.05; 95% CI, 1.94-4.79; P < 0.05）。001)和DFS (HR 1.79; 95%可信区间,1.13 - -2.85;P = . 01)。在这项队列研究中，KRAS变异亚型的分布特征在来自中国的大型ICC患者队列中得到了表征。G12 KRAS变异而非G12 KRAS变异的存在与较差的生存和复发风险增加相关。G12V变异的患者在整个队列中表现出最差的结果。
What is the prevalence of KRAS variant subtypes and their association with survival and recurrence in patients with surgically treated intrahepatic cholangiocarcinoma (ICC)? In this cohort study including 1024 patients, a total of 14 different subtypes of KRAS somatic variants affecting 127 patients with ICC (12.4%) were identified, including G12D (43.3%), G12V (19.7%), G12C (7.1%), and G13D (6.3%). G12 KRAS variants but not non-G12 KRAS variants were independently associated with worse overall and disease-free survival, and the G12V KRAS variant was the strongest prognostic determinant for the worst overall and disease-free survival. This cohort study characterized the distribution of KRAS variant subtypes in a large cohort of patients with ICC and showed an association with patient outcome. This cohort study explores the prognostic association of KRAS variant subtypes with survival and recurrence in patients with intrahepatic cholangiocarcinoma. KRAS variants are associated with tumor progression; however, the prevalence of KRAS variant subtypes and their association with survival and recurrence in patients with intrahepatic cholangiocarcinoma (ICC) after curative resection are largely unknown. To explore the prognostic association of KRAS variant subtypes with survival and recurrence in patients with ICC. In this cohort study, patients who underwent curative resection for ICC from January 2009 through December 2016 at a single hospital in China were recruited, and whole-exome sequencing, targeted sequencing, and Sanger sequencing were performed to identify KRAS variants. Kaplan-Meier and log-rank tests were used to compare overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. Data were analyzed from April 2020 to January 2021. Hepatectomy in patients with ICC. The association of KRAS variant subtypes with OS and DFS. Of 1024 included patients with ICC, 621 (60.6%) were male, and the mean (SD) age was 59.2 (10.2) years. A total of 14 different subtypes of KRAS somatic variants affecting 127 patients (12.4%) were identified. G12D was the most frequent allele in this cohort, accounting for 55 of 127 identified KRAS variants (43.3%), followed by G12V (25 [19.7%]), G12C (9 [7.1%]), and G13D (8 [6.3%]). Compared with patients with wild-type KRAS, patients with variant KRAS were more likely to have high levels of carbohydrate antigen 19-9 (92 of 127 [72.4%] vs 546 of 897 [60.9%]; P = .01) and γ-glutamyltransferase (72 of 127 [56.7%] vs 420 of 897 [46.8%]; P = .04). Multivariable analysis revealed that G12 KRAS variants but not non-G12 KRAS variants were independently associated with worse OS (hazard ratio [HR], 1.69; 95% CI, 1.31-2.18; P < .001) and DFS (HR, 1.47; 95% CI, 1.16-1.88; P = .002). Among the patients with G12 KRAS variants, the G12V KRAS variant was the strongest prognostic determinant for the worst OS (HR, 3.05; 95% CI, 1.94-4.79; P < .001) and DFS (HR, 1.79; 95% CI, 1.13-2.85; P = .01). In this cohort study, the distribution of KRAS variant subtypes was characterized in a large cohort of patients with ICC from China. The presence of G12 KRAS variants but not non-G12 KRAS variants was associated with worse survival and increased risk of recurrence. Patients with the G12V variant exhibited the worst outcomes in the whole cohort.
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