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KRAS基因突变在结直肠癌中的预后意义——初步研究

Prognostic significance of KRAS gene mutations in colorectal cancer--preliminary study.

作者信息

Dinu D, Dobre M, Panaitescu E, Bîrlă R, Iosif C, Hoara P, Caragui A, Boeriu M, Constantinoiu S, Ardeleanu C

机构信息

General and Oesophagial Surgical Department, "Carol Davila" University of Medicine and Pharmacy; "Sf. Maria" Clinical Hospital, Bucharest, Romania.

Department of Pathology, "Victor Babes" National Institute for Research and Development in Pathology and Biomedical Sciences, Bucharest, Romania ; University of Bucharest, Faculty of Biology, Bucharest, Romania.

出版信息

J Med Life. 2014 Oct-Dec;7(4):581-7.

Abstract

OBJECTIVE

The prognostic significance of KRAS gene mutations, evaluated by using two methods in patients with colorectal cancer (CRC).

MATERIAL AND METHODS

Retrospective study involving 58 patients diagnosed with CRC and treated between 2003 and 2010 in the General and Esophageal Surgery Clinic of "Sf. Maria" Hospital, Bucharest. The macroscopic and microscopic examination of the resected specimens was also processed for genetic analysis in NIRDPBS, where KRAS status was determined by using two methods: PCR-RFLP and pyrosequencing.

RESULTS

The clinical and biological parameters of the patients were assessed for 72 months in average. A relapse in 21 patients and a 5-year survival rate of 79.3% was discovered. The genetic analyses of KRAS gene found mutations in 22 cases (45.3%): 17 cases had mutations in codon 12, 5 cases in codon 13. The survival rate analyses of patients with wild KRAS gene compared with the patients carrying the mutation on codon 12 /13 revealed a superposition of the survival curve. The statistical analysis based on the TNM stage revealed different survival curves in stage I and II, shorter survival period in patients with KRAS mutation on codon 13 than in those with wild type gene (stage I--p_value=0.015; stage II--p_value=0.000).

CONCLUSIONS

It was not found that KRAS gene status had any prognostic significance. Nevertheless, for stage I and II patients, the mutation found on codon 13 determined a statistic significant shorter survival rate than for those with wild type. The results obtained by using the pyrosequencing method for the determination of KRAS gene status proved that it represented a reliable and reproducible method.

摘要

目的

采用两种方法评估结直肠癌(CRC)患者中KRAS基因突变的预后意义。

材料与方法

回顾性研究纳入了2003年至2010年在布加勒斯特“Sf. Maria”医院普通外科和胸外科诊所诊断并接受治疗的58例CRC患者。对切除标本进行宏观和微观检查,并在国家肿瘤疾病预防与控制研究所进行基因分析,通过两种方法确定KRAS状态:聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和焦磷酸测序。

结果

对患者的临床和生物学参数平均评估了72个月。发现21例患者复发,5年生存率为79.3%。KRAS基因的基因分析发现22例(45.3%)存在突变:17例密码子12发生突变,5例密码子13发生突变。野生型KRAS基因患者与密码子12/13携带突变患者的生存率分析显示生存曲线重叠。基于TNM分期的统计分析显示I期和II期生存曲线不同,密码子13发生KRAS突变的患者生存期短于野生型基因患者(I期——p值=0.015;II期——p值=0.000)。

结论

未发现KRAS基因状态具有任何预后意义。然而,对于I期和II期患者,密码子13发现的突变确定其生存率在统计学上显著短于野生型患者。采用焦磷酸测序法测定KRAS基因状态所获得的结果证明该方法是一种可靠且可重复的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d6/4316144/31cc9df46cb2/JMedLife-07-581-g001.jpg

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