de Juan C, Iniesta P, Vega F J, Peinado M A, Fernandez C, Caldés T, Massa M J, López J A, Sánchez A, Torres A J, Balibrea J L, Benito M
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Br J Cancer. 1998 Jun;77(11):1971-7. doi: 10.1038/bjc.1998.327.
Genomic alterations have been analysed in 65 non-small-cell lung cancer (NSCLC) tissue samples by using the arbitrarily primed polymerase chain reaction (AP-PCR), which is a PCR-based genomic fingerprinting. We have shown that AP-PCR may be applied as a useful and feasible practical method for detection of the genomic alterations that accompany malignancy in NSCLC. Genomic changes detected by us consisted of: allelic losses or gains in anonymous DNA sequences, homozygously deleted DNA sequences and polymorphic DNA sequences. According to these genomic changes, lung tumours evaluated in the present study have been scored into three groups: low, moderate and high genomic damage tumours. The aim of this study was to investigate the effect of genomic damage on patient survival. Survival analysis was carried out in 51 NSCLC patients. Our results revealed that high genomic damage patients showed a poorer prognosis than those with low or moderate genomic damage (P = 0.038). Multivariate Cox regression analysis showed that patients with higher genomic alterations displayed an adjusted-by-stage risk ratio 4.26 times higher than the remaining patients (95% CI = 1.03-17.54). We can conclude that genomic damage has an independent prognostic value of poor clinical evolution in NSCLC.
通过使用任意引物聚合酶链反应（AP-PCR，一种基于PCR的基因组指纹分析技术），对65份非小细胞肺癌（NSCLC）组织样本的基因组改变进行了分析。我们已经表明，AP-PCR可作为一种有用且可行的实用方法，用于检测NSCLC中伴随恶性肿瘤发生的基因组改变。我们检测到的基因组变化包括：匿名DNA序列中的等位基因缺失或增加、纯合缺失的DNA序列以及多态性DNA序列。根据这些基因组变化，本研究中评估的肺肿瘤被分为三组：低基因组损伤肿瘤、中等基因组损伤肿瘤和高基因组损伤肿瘤。本研究的目的是调查基因组损伤对患者生存的影响。对51例NSCLC患者进行了生存分析。我们的结果显示，高基因组损伤患者的预后比低或中等基因组损伤患者更差（P = 0.038）。多变量Cox回归分析表明，基因组改变较高的患者经分期调整后的风险比是其余患者的4.26倍（95%置信区间 = 1.03 - 17.54）。我们可以得出结论，基因组损伤在NSCLC中对不良临床进展具有独立的预后价值。
