Mutational analysis of KRAS and its clinical implications in cervical cancer patients.

Mutational analysis of KRAS and its clinical implications in cervical cancer patients.
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宫颈癌患者 KRAS 突变分析及其临床意义。

DOI:
10.3802/jgo.2018.29.e4
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发表时间:
2018-01
影响因子:
3.9
通讯作者:
Yang H
Yang H
中科院分区:
医学2区
文献类型:
--
作者:
Jiang W;Xiang L;Pei X;He T;Shen X;Wu X;Yang H

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KRAS突变在宫颈癌中的预测和预后作用仍然没有定论。本研究的目的是探讨浸润性宫颈癌(ICC)中KRAS突变的临床病理学和预后相关性。采用逆转录聚合酶链反应(PCR)和桑格测序法检测876例ICC患者KRAS基因突变。采用实时荧光定量PCR检测人乳头瘤病毒(HPV)16型和18型。在30例(3.4%)患者中发现了KRAS的非同义突变。这些突变在非鳞状细胞癌中比鳞状细胞癌(SCC)中更常见(分别为8.2%和2.2%,p<0.001),并与HPV 18感染相关(p=0.003)。在不常见的组织学亚型中,突变的患病率最高(18.2%),其次是腺癌(AC,7.3%)和腺鳞癌(ASC,5.8%)。在55个月的中位随访期间,与野生型KRAS患者相比,突变型KRAS患者复发的百分比更高(分别为20.0%和42.9%,p=0.007)。KRAS突变患者的3年无复发生存率低于无KRAS突变患者(分别为57.1%和81.9%,p=0.001)。此外,多变量分析显示,KRAS突变的存在是疾病复发的独立预测因子(风险比[HR]=2.064; 95%置信区间[CI]=1.125-3.787; p=0.019)。KRAS突变在宫颈非SCC中占主导地位,并与HPV 18感染相关。KRAS突变检测和HPV基因分型的组合将有助于识别预后不良的患者,以进行进一步干预。
The predictive and prognostic role of KRAS mutations in cervical cancer remains inconclusive. The aim of this study was to explore the clinicopathological and prognostic relevance of KRAS mutations in invasive cervical cancers (ICC). Reverse transcription polymerase chain reaction (PCR) and Sanger sequencing were employed to detect KRAS mutations in 876 ICC patients. Quantitative real-time PCR was used to detect human papillomavirus (HPV) 16 and HPV 18. Non-synonymous mutations of KRAS were identified in 30 (3.4%) patients. These mutations were more common in non-squamous cell carcinoma than in squamous cell carcinoma (SCC) (8.2% vs. 2.2%, respectively, p<0.001) and were associated with HPV 18 infection (p=0.003). The prevalence of mutations was highest (18.2%) in the uncommon histological subtypes followed by adenocarcinoma (AC, 7.3%) and adenosquamous carcinoma (ASC, 5.8%). During the median follow-up of 55 months, compared to patients with wild-type KRAS, a greater percentage of patients with mutant KRAS relapsed (20.0% vs. 42.9%, respectively, p=0.007). The 3-year relapse-free survival was poorer in patients with mutant KRAS than in patients without KRAS mutations (57.1% vs. 81.9%, respectively, p=0.001). Furthermore, the multivariate analysis showed that the presence of a KRAS mutation was an independent predictor for disease recurrence (hazard ratio [HR]=2.064; 95% confidence interval [CI]=1.125–3.787; p=0.019). KRAS mutations were predominant in non-SCCs of the cervix and were associated with HPV 18 infection. A combination of KRAS mutation detection and HPV genotyping would be useful in identifying patient with poor prognosis for further interventions.
K-RAS基因突变在结直肠腺瘤进展中的作用的详细分析。
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发表时间: 1997
影响因子: 8.8
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DOI: 10.18632/oncotarget.3212
发表时间: 2015-03-10
期刊: Oncotarget
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期刊: Nature reviews. Cancer
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