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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(G>A)(P=0.017,OR:0.67,95%CI:0.49~0.93)和rs12303764(A>C)(P=0.009,OR:0.63,95%CI:0.45-0.89)及位于ATG14基因上的位点rs17742719(C>A)(P=0.002,OR:1.83,95%CI:1.26~2.66)、rs8003279(A>G)(P=0.006,OR:1.65,95%CI:1.16~2.35)和rs1009647(G>A)(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(G>A)(P=0.004,HR:0.63;95%CI:0.46~0.86)和rs17032060(G>A)(P=0.006,HR:0.65,95%CI:0.48~0.88)及位于ATG3基因上的位点rs13082005(G>A)(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(G>A)(P=0.011,HR:0.74,95%CI:0.58~0.93)和位于ATG10基因上的位点rs1864183(G>A)(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。
The use of platinum-containing chemotherapy in patients with advanced non-small cell lung cancer is a very important clinical treatment of lung cancer, however, there is a clear individual difference in the sensitivity of different patients to platinum-based chemotherapy, suggesting that potential molecular markers are important for predicting clinical Platinum-containing chemotherapy in the treatment of a key role. The purpose of this study was to explore the association between autophagy pathway gene polymorphisms and the efficacy of platinum-based chemotherapy for advanced non-small cell lung cancer in order to find molecular markers that may affect the sensitivity of platinum-containing chemotherapeutics. This study enrolled 1004 patients with advanced non-small cell lung cancer who underwent platinum-based chemotherapy and analyzed 99 SNP loci on 13 genes in the autophagic pathway in relation to the clinical benefit of platinum-containing chemotherapy, time to disease-free progression, and overall survival The correlation between. The results showed that rs7953348 (G> A) (P = 0.017, OR: 0.67, 95% CI: 0.49-0.93) and rs12303764 (A> CI: 0.45-0.89) and rs17742719 (C> A) (AT = 0.002, OR: 1.83, 95% CI: 1.26-2.66) and rs8003279 (A> : 1.65, 95% CI: 1.16 to 2.35) and rs1009647 (G> A) (P = 0.002, OR: 1.70, 95% CI: 1.22 to 2.37) were significantly associated with clinical benefit at the site of the DRAM gene rs7955890 (P> 0.004, HR: 0.63; 95% CI: 0.46-0.86) and rs17032060 (G> A) The loci of rs13082005 (G> A) (P = 0.012, HR: 1.27, 95% CI: 1.05-1.53) were significantly correlated with the progression-free time of platinum- (P = 0.011, HR: 0.74, 95% CI: 0.58-0.93) and locus rs1864183 (G> A) The platinum-containing chemotherapy has a significant impact on the total survival time. The results suggest that autophagy pathway plays an important role in the sensitivity of platinum-containing chemotherapy. The genetic polymorphism of autophagy pathway may be a potential molecular marker for predicting the efficacy of platinum-based chemotherapy. This may provide some evidence for the personalized medical treatment of lung cancer The theoretical basis.