Zhao Hua, Shen Jie, Deininger Prescott, Hunt Jay D
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
Cancer Lett. 2007 Feb 8;246(1-2):47-53. doi: 10.1016/j.canlet.2006.01.031. Epub 2006 Mar 6.
Apurinic/apyrimidinic (AP or abasic) sites are common DNA lesions that arise from spontaneous depurination or by base excision repair (BER) of modified bases. Accumulation of impaired AP sites could lead to increased genomic instability that in turn could lead to a more malignant phenotypic behavior of tumors. We, therefore, evaluated the effects of AP sites on survival in resected non-small cell lung cancer (NSCLC) patients. Resected tumor specimens from 99 patients with NSCLC who underwent surgical resection were collected. The enzyme-linked immunosorbent assay was applied to measure the levels of AP sites in tumor DNA. The median number of AP sites per 10(5) nucleotides was 12.4 for all the study subjects. Patients with low levels of AP site had significantly longer survival time compared with ones with medium or high levels of AP site (log-rank test: P=0.015). In Cox regression analysis, patients with medium or high levels of AP sites had over twofold increased hazard of death. In addition, we found a statistically significant correlation between levels of AP sites and age (rho=0.560, P<0.001). The results of this study demonstrated that levels of AP sites could predict survival in resected NSCLC patients. We postulate that an intact BER mechanism may reduce the accumulation of oxidative DNA damage that are thought to contribute to the tumor's malignant potential and therefore the risk of death.
脱嘌呤/脱嘧啶(AP或无碱基)位点是常见的DNA损伤,其源于自发脱嘌呤或通过对修饰碱基的碱基切除修复(BER)产生。受损AP位点的积累可能导致基因组不稳定性增加,进而可能导致肿瘤更具恶性的表型行为。因此,我们评估了AP位点对接受手术切除的非小细胞肺癌(NSCLC)患者生存的影响。收集了99例接受手术切除的NSCLC患者的切除肿瘤标本。应用酶联免疫吸附测定法测量肿瘤DNA中AP位点的水平。所有研究对象每10⁵个核苷酸中AP位点的中位数为12.4。AP位点水平低的患者与AP位点水平中等或高的患者相比,生存时间显著更长(对数秩检验:P = 0.015)。在Cox回归分析中,AP位点水平中等或高的患者死亡风险增加了两倍多。此外,我们发现AP位点水平与年龄之间存在统计学显著相关性(rho = 0.560,P < 0.001)。本研究结果表明,AP位点水平可以预测接受手术切除的NSCLC患者的生存情况。我们推测,完整的BER机制可能会减少氧化DNA损伤的积累,而氧化DNA损伤被认为会导致肿瘤的恶性潜能增加,从而增加死亡风险。