中国结直肠癌患者KRAS突变的临床特征及预后价值

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

International Journal of Biological Markers Pub Date : 2021-06-01 Epub Date: 2021-05-27 DOI:10.1177/17246008211017152

Ye Yuan, Yingting Liu, Ye Wu, Junling Zhang, Chunti Shen, Feng Zhang, Changping Wu, Wenwei Hu

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引用次数: 5

摘要

背景:KRAS突变是在西方和亚洲国家的结直肠癌患者中发现的高频体细胞突变，然而，除了KRAS外显子2外，其他的患病率和预后价值尚未在亚洲患者中得到充分的评估。本研究旨在确定中国结直肠癌患者KRAS全外显子突变的突变频率，并探讨其对预后的影响。方法:对7189份肿瘤组织样本(iCohort)进行新一代测序，检测KRAS突变。考虑KRAS的所有病理性或可能的病理性突变。此外，收集中国苏州大学第三附属医院(sCohort) 145例患者的临床特征和预后数据，并使用液滴数字™聚合酶链反应检测KRAS突变。结果:在i组中，2706例(37.6%)患者被证实携带KRAS突变。G12D(32.19%)、G12V(17.96%)和G13D(17.59%)是最常见的突变。在sCohort中，51例结直肠癌患者(35.17%)存在KRAS突变，其中KRAS G12D(64.71%)、G13D(29.41%)和G14D(3.92%)频率较高。KRAS突变与野生型肿瘤相比，中位总生存期较短(69个月对55个月;人力资源1.80;95% Cl 1.22, 2.64;P = 0.0003)。Cox多因素分析中，年龄(HR 1.562;95% Cl 1.10, 2.22;P=0.013)，肿瘤分化(HR 0.417;95% Cl = 0.19, 0.90;P=0.026)， KRAS突变(HR 1.897;95% Cl = 0.19, 0.90;P=0.001)仍然是较短总生存期的独立预测因子。在常见的KRAS突变中，G12D与较短的总生存期显著相关(HR 2.17;95% Cl 1.31, 3.58;P < 0.0001)，与KRAS野生型患者相比。结论:我们的研究结果表明，KRAS基因突变频繁，超过30%的KRAS G12D突变亚型。我们发现KRAS G12D突变与低生存率相关，是中国患者预后不良的生物标志物。我们的数据强调了分子特征在结直肠癌患者中的重要性，这些特征可能通过g12d特异性相关抑制剂得到改善。

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Clinical characteristics and prognostic value of the KRAS mutation in Chinese colorectal cancer patients.

Background: The KRAS mutations are high-frequency somatic mutations found in colorectal cancer patients from Western and Asian countries however, with the exception of exon 2 of KRAS, other prevalence and prognostic values have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of whole exon mutations of KRAS in Chinese colorectal cancer patients and to investigate their impact on prognosis.

Methods: A total of 7189 tumor tissue samples (iCohort) were subjected to next-generation sequencing for detection of KRAS mutations. All pathologic or likely pathologic mutations of KRAS were considered. In addition, clinical features and prognostic dates were collected from 145 patients at The Third Affiliated Hospital of Soochow University, China (sCohort) and used droplet digital™ polymerase chain reaction to detect KRAS mutations.

Results: In the iCohort, 2706 patients (37.6%) were confirmed harboring KRAS mutations. The most frequent of these mutations were G12D (32.19%), G12V (17.96%), and G13D (17.59%). In the sCohort, 51 colorectal cancer patients (35.17%) had KRAS mutations, among which KRAS G12D (64.71%), G13D (29.41%), and G14D (3.92%) were high-frequency. The KRAS mutations were associated with shorter median overall survival than wild-type tumors (69 vs. 55 months; HR 1.80; 95% Cl 1.22, 2.64; P=0.0003). In the Cox multivariate analysis, age (HR 1.562; 95% Cl 1.10, 2.22; P=0.013), tumor differentiation (HR 0.417; 95% Cl 0.19, 0.90; P=0.026), and KRAS mutation (HR 1.897; 95% Cl 0.19, 0.90; P=0.001) remained independent predictors of shorter overall survival. Among the common KRAS mutations, G12D was significantly associated with shorter overall survival (HR 2.17; 95% Cl 1.31, 3.58; P < 0.0001) compared with KRAS wild-type patients.

Conclusions: Our findings indicate that KRAS genes are frequently mutated, and over 30% harbored the KRAS G12D mutation subtype. We found that the KRAS G12D mutation is associated with inferior survival and is a biomarker of poor prognosis in Chinese patients. Our data emphasize the importance of molecular features in colorectal cancer patients, which could potentially be improved by G12D-specific related inhibitors.

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来源期刊

International Journal of Biological Markers 医学-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

期刊介绍： IJBM is an international, online only, peer-reviewed Journal, which publishes original research and critical reviews primarily focused on cancer biomarkers. IJBM targets advanced topics regarding the application of biomarkers in oncology and is dedicated to solid tumors in adult subjects. The clinical scenarios of interests are screening and early diagnosis of cancer, prognostic assessment, prediction of the response to and monitoring of treatment.