Chang Ya-Sian, Chang Shun-Jen, Yeh Kun-Tu, Lin Tsai-Hsiu, Chang Jan-Gowth
Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan.
Onkologie. 2013;36(12):719-24. doi: 10.1159/000356814. Epub 2013 Nov 20.
Colorectal cancer (CRC) plays an important role in cancer mortality and morbidity. This study examined colorectal tissues for RAS, BRAF, and TP53 gene mutations to assess their value as indicators of outcomes of CRC therapy.
DNA was extracted from tissues taken from 165 patients with CRC. RAS gene mutations (exons 2 and 3) were detected by primer extension analysis. BRAF gene mutations (V600E) were detected by high resolution melting (HRM) analysis. TP53 gene mutations (exons 5-8) were detected by direct sequencing.
RAS, BRAF, and TP53 mutations occurred in 36.97% (61/165), 4.24% (7/165), and 37.58% (62/165), respectively. The KRAS mutation is a predictor for poor 5-year survival (p = 0.05), and the co-presence of KRAS and TP53 mutations correlates with lymph node involvement (p = 0.029), tumor stage (p = 0.029), and poor survival (p = 0.021). Multivariate analysis adjusted for tumor size, histologic grade, lymph node metastasis, sex, and age also indicated that KRAS mutations correlate significantly with overall survival (p = 0.036).
The KRAS mutation is not present in about one-third of CRC patients, and therefore other gene mutations need to be investigated to better understand the molecular mechanisms of CRC and its treatment.
结直肠癌(CRC)在癌症死亡率和发病率中起着重要作用。本研究检测了结直肠组织中的RAS、BRAF和TP53基因突变,以评估它们作为CRC治疗结果指标的价值。
从165例CRC患者的组织中提取DNA。通过引物延伸分析检测RAS基因突变(外显子2和3)。通过高分辨率熔解(HRM)分析检测BRAF基因突变(V600E)。通过直接测序检测TP53基因突变(外显子5 - 8)。
RAS、BRAF和TP53基因突变分别发生在36.97%(61/165)、4.24%(7/165)和37.58%(62/165)的患者中。KRAS突变是5年生存率低的一个预测指标(p = 0.05),KRAS和TP53突变同时存在与淋巴结受累(p = 0.029)、肿瘤分期(p = 0.029)及生存率低(p = 0.021)相关。对肿瘤大小、组织学分级、淋巴结转移、性别和年龄进行校正的多因素分析也表明,KRAS突变与总生存期显著相关(p = 0.036)。
约三分之一的CRC患者不存在KRAS突变,因此需要研究其他基因突变,以更好地了解CRC的分子机制及其治疗方法。