Correlation of K-ras codon 12 mutations in human feces and ages of patients with colorectal cancer (CRC)
Correlation of K-ras codon 12 mutations in human feces and ages of patients with colorectal cancer (CRC)
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DOI：
10.1016/j.trsl.2006.09.006
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发表时间：
2007-02-01
影响因子：
7.8
通讯作者：
Huang, Chi-Jung
中科院分区：
文献类型：
--
作者：
Chien, Chih-Cheng;Chen, Shu-Hung;Huang, Chi-Jung
结直肠癌(CRC)是主要的胃肠道恶性肿瘤，在世界范围内构成了主要的医疗和经济负担。彻底了解癌基因或与肿瘤发生相关的基因是制定成功治疗策略的关键。粪便的分子分析构成了一种潜在的有效和非侵入性的检测结直肠癌的方法。应用巢式逆转录聚合酶链式反应(RT-PCR)和扩增限制性片段长度多态性分析方法，分析了来自结肠和直肠全长的脱落细胞中激活的K-ras密码子12突变体的表达，这些突变体正成为反义治疗的有吸引力的靶点。在5%(1/20)健康对照粪便、41%(12/29)结直肠癌患者粪便、10%(3/29)组织互补DNA分离株、14%(4/29)基因组DNA分离株中检测到K-ras密码子12突变序列。患者年龄与粪便中K-ras密码子12序列显著相关：野生型K-ras密码子12序列患者显著低于突变K-ras密码子12序列患者。粪便核糖核酸(RNA)分析是诊断结直肠癌的有用方法。该技术可能适用于粪便中K-ras基因活性突变的筛选和临床意义的确定，并可能有助于识别将受益于反义治疗的患者。
Colorectal cancer (CRC) is the predominant gastrointestinal malignancy and constitutes a major medical and economic burden worldwide. A thorough understanding of the oncogenes or genes related to tumorigenesis is the key to developing successful therapeutic strategies. Molecular analysis of feces constitutes a potentially potent and noninvasive method for detection of CRC. Using nested reverse transcription-polymerase chain reaction (RT-PCR) and amplified restriction fragment length polymorphism analysis, sloughed cells from the entire length of the colon and rectum were analyzed for expression of activating K-ras codon 12 mutants, which are becoming attractive targets for antisense treatment. K-ras codon 12 mutant sequences were detected in feces of 5% (1/20) of healthy controls, in feces of 41% (12/29) of CRC patients, in 10% (3/29) of isolates of tissue complementary DNA (cDNA), and in 14% (4/29) of isolates of genomic DNA. Age of patient was significantly associated with K-ras codon 12 sequences in feces: Patients with wild-type K-ras codon 12 sequences were significantly younger than those with mutated forms of K-ras codon 12. Fecal ribonucleic acid (RNA) analysis was demonstrated to be a useful for diagnosis of CRC. This technique may be suitable for screening and determinatign the clinical significance of active mutations of the K-ras gene in feces and would possibly be useful for identificating patients that would benefit from antisense therapy.