自噬通路基因多态性与晚期非小细胞肺癌含铂化疗疗效的相关性分析

发布时间：2018-12-15 07:27

【摘要】：对晚期非小细胞肺癌患者采用含铂化疗是肺癌临床治疗中非常重要的方法,然而不同患者对含铂化疗的敏感性却存在着明显的个体差异,这提示发现潜在的分子标志物对预测临床中含铂化疗疗效具有关键作用。本研究旨在探索自噬通路基因多态性与晚期非小细胞肺癌含铂化疗疗效之间的相关性,以期寻找可能影响含铂化疗药物敏感性的分子标记。本研究纳入了1004例接受含铂化疗的晚期非小细胞肺癌患者,分析了自噬通路中13个基因上的99个SNP位点与含铂化疗临床获益、无疾病进展时间及总生存时间之间的相关性。研究发现,位于ULK1基因的位点rs7953348(GA)(P=0.017,OR:0.67,95%CI:0.49~0.93)和rs12303764(AC)(P=0.009,OR:0.63,95%CI:0.45-0.89)及位于ATG14基因上的位点rs17742719(CA)(P=0.002,OR:1.83,95%CI:1.26~2.66)、rs8003279(AG)(P=0.006,OR:1.65,95%CI:1.16~2.35)和rs1009647(GA)(P=0.002,OR:1.70,95%CI:1.22~2.37)与临床获益存在显著关联,位于DRAM基因上的位点rs7955890(GA)(P=0.004,HR:0.63;95%CI:0.46~0.86)和rs17032060(GA)(P=0.006,HR:0.65,95%CI:0.48~0.88)及位于ATG3基因上的位点rs13082005(GA)(P=0.012,HR:1.27,95%CI:1.05~1.53)与含铂化疗的无疾病进展时间显著相关,位于ULK1基因的位点rs7953348(GA)(P=0.011,HR:0.74,95%CI:0.58~0.93)和位于ATG10基因上的位点rs1864183(GA)(P=0.016,HR:0.42,95%CI:0.21~0.85)对含铂化疗的总生存时间有着显著影响。研究结果提示自噬通路在含铂化疗敏感性中发挥着重要作用,自噬通路基因多态性可能是预测含铂化疗疗效的潜在分子标志物,这可能为临床上肺癌的个体化医疗提供一定的理论基础。
[Abstract]:Chemotherapy with platinum in patients with advanced non-small cell lung cancer (NSCLC) is a very important method in the clinical treatment of lung cancer. However, there are significant individual differences in the sensitivity of different patients to chemotherapy with platinum. It suggests that the discovery of potential molecular markers plays a key role in predicting the clinical efficacy of platinum-containing chemotherapy. The aim of this study was to explore the relationship between autophagy pathway gene polymorphism and chemotherapy efficacy of platinum in advanced non-small cell lung cancer (NSCLC), in order to search for molecular markers that may affect the chemosensitivity of advanced non-small cell lung cancer (NSCLC). A total of 1004 patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy with platinum were included in this study. The correlation between 99 SNP loci of 13 genes in autophagy pathway and clinical benefit, disease free progression time and total survival time of platinum containing chemotherapy was analyzed. The study found that rs7953348 (GA) (P0. 017O: 0.6795 CI: 0. 490.93) and rs12303764 (AC) (P0. 009 are located at the site of the ULK1 gene. OR:0.63,95%CI:0.45-0.89) and the ATG14 gene rs17742719 (CA) (Pu 0.002 or: 1.83 or 95 CI: 1.262.66), rs8003279 (AG) (Pu 0.006, OR:1.65,95%CI:1.16~2.35) and rs1009647 (GA) (Pu 0.002 OR: 1.70,95 CI: 1.222.37) were significantly associated with clinical benefits, and the site on the DRAM gene, rs7955890 (GA) (Pao 0.004, HR: 0.63; 95%CI:0.46~0.86) and rs17032060 (GA) (Pu 0.006 and rs13082005 (GA) (Pu 0.012, which is located on the ATG3 gene, and rs17032060 (GA) (: 0.65-95 CI: 0.480.88). HR:1.27,95%CI:1.05~1.53) was significantly correlated with the time of disease progression in platinum-containing chemotherapy, and was located at rs7953348 (GA) (Pu 0.011, the site of the ULK1 gene. HR:0.74,95%CI:0.58~0.93) and the locus rs1864183 (GA) (P0. 016 on the ATG10 gene had significant effects on the total survival time of platinum containing chemotherapy, including 0. 42% and 95% CI: 0. 21 0. 85). The results suggest that autophagy pathway plays an important role in chemosensitivity to platinum, and autophagy pathway gene polymorphism may be a potential molecular marker for predicting the efficacy of chemotherapy with platinum. This may provide a theoretical basis for clinical individualized treatment of lung cancer.
【作者单位】：复旦大学生命科学学院遗传工程国家重点实验室;同济大学附属肺科医院;上海市刑事科学技术研究院;第二军医大学附属长海医院;上海交通大学附属胸科医院;复旦大学附属中山医院;
【基金】：国家自然科学基金项目(编号:81372235,31571371) 国家高技术研究发展计划(863计划)项目(编号:2012AA02A518)资助~~
【分类号】：R734.2

【相似文献】