Bisgaard M L, Jäger A C, Dalgaard P, Søndergaard J O, Rehfeld J F, Nielsen F C
Dept. of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
Scand J Gastroenterol. 2001 Apr;36(4):405-9. doi: 10.1080/003655201300051252.
Since allelic loss of genes involved in the development of colorectal cancer could serve as prognostic markers, we examined the correlation between loss of markers linked to the hMSH2/hMSH6 (2p21-16.3), hMLH1 (3p21.3), APC (5q21-22), p53 (17p13.1) and DCC (18q21.3) loci and survival in a series of 64 consecutively collected colorectal cancers.
The association between allelic loss and survival was analysed by univariate and multivariate tests to identify independent variables of survival.
Loss of chromosome 2p21-16.3 reduced the overall 5-year survival from 52% to 15% (P = 0.0003). The prognostic significance was evident in patients with Dukes' A + B as well as Dukes' C tumours. A multivariate analysis comparing Dukes' staging, age at diagnosis, tumour localization, sex, loss of chromosome 2p21-16.3, 3p21.3, 5q21-22, 17p13.1 or 18q21.3 and microsatellite instability showed that only Dukes' staging (hazard ratio 3.0; 1.4-6.5 with 95% confidence interval, P = 0.0065) and loss of 2p21-16.3 (hazard ratio 6.2; 2.3-16.8 with 95% confidence interval, P = 0.0006) were independent variables of survival. Loss of 2p21-16.3 was, moreover, associated with increased loss of the other tumour suppressor loci (P = 0.012).
The results show that loss of 2p21-16.3 is an independent indicator of survival in patients with colorectal cancer.
由于参与结直肠癌发生发展的基因的等位基因缺失可作为预后标志物,我们在一系列连续收集的64例结直肠癌中,研究了与hMSH2/hMSH6(2p21 - 16.3)、hMLH1(3p21.3)、APC(5q21 - 22)、p53(17p13.1)和DCC(18q21.3)基因座相关的标志物缺失与生存之间的相关性。
通过单因素和多因素检验分析等位基因缺失与生存之间的关联,以确定生存的独立变量。
2p21 - 16.3染色体缺失使总体5年生存率从52%降至15%(P = 0.0003)。这种预后意义在Dukes' A + B期以及Dukes' C期肿瘤患者中均很明显。一项多因素分析比较了Dukes分期、诊断时年龄、肿瘤定位、性别、2p21 - 16.3、3p21.3、5q21 - 22、17p13.1或18q21.3染色体缺失以及微卫星不稳定性,结果显示只有Dukes分期(风险比3.0;95%置信区间为1.4 - 6.5,P = 0.0065)和2p21 - 16.3缺失(风险比6.2;95%置信区间为2.3 - 16.8,P = 0.0006)是生存的独立变量。此外,2p21 - 16.3缺失与其他肿瘤抑制基因座的缺失增加相关(P = 0.012)。
结果表明,2p21 - 16.3缺失是结直肠癌患者生存的独立指标。