Lee J C, Wang S T, Lai M D, Lin Y J, Yang H B
Department of Surgery, National Cheng-Kung University Hospital, Tainan, Taiwan, Republic of China.
Anticancer Res. 1996 Nov-Dec;16(6B):3839-44.
Mutations in the K-ras gene were found to be of predictive value in the clinical outcome of non-small cell lung cancers, but its role in predicting the survival of colorectal cancer patients is still inconclusive. Point mutations in codon 12 or 13 of K-ras gene were analyzed in 64 colorectal cancers composing 4 Dukes' stage. A, 34 stage B, 21 stage C and 5 stage D. DNA extracted from the paraffin-embedded tissues of the 64 patients was amplified with the polymerase chain reaction and subsequently analyzed by direct cycle sequencing. Thirteen of sixty-four (20%) resected colorectal cancer specimens were found to have K-ras gene mutation at either codon 12 or 13. Log rank tests found that K-ras gene mutation and Dukes' stage were associated with patients' survival. When stratified by Dukes' stage, the patients with mutated K-ras genes in the stratum of stage A or B were found to have shorter survival times than those without mutated K-ras genes (P = 0.003), but this was not the case in the stratum of stages C and D. The relative risk of mortality in the stratum of stage A or B was 7.74 (95% confidence interval: 1.72-34.89) by Cox regression analysis. We thereby conclude that K-ras gene mutation is a usefull predictor of the survival of early stage colorectal cancers.
研究发现，K-ras基因的突变对非小细胞肺癌的临床预后具有预测价值，但其在预测结直肠癌患者生存情况中的作用仍尚无定论。对64例处于4个Dukes分期（A期34例、B期21例、C期21例、D期5例）的结直肠癌患者的K-ras基因第12或13密码子的点突变情况进行了分析。从64例患者石蜡包埋组织中提取的DNA经聚合酶链反应扩增，随后通过直接循环测序进行分析。64例切除的结直肠癌标本中，有13例（20%）在第12或13密码子处存在K-ras基因突变。对数秩检验发现，K-ras基因突变和Dukes分期与患者生存相关。按Dukes分期分层时，发现A期或B期有K-ras基因突变的患者的生存时间短于无K-ras基因突变的患者（P = 0.003），但在C期和D期则不然。通过Cox回归分析，A期或B期的相对死亡风险为7.74（95%置信区间：1.72 - 34.89）。因此，我们得出结论，K-ras基因突变是早期结直肠癌生存的有用预测指标。
