Genetic profiling-based prognostic prediction of patients with advanced small-cell lung cancer in large scale analysis
Genetic profiling-based prognostic prediction of patients with advanced small-cell lung cancer in large scale analysis
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DOI：
10.1016/j.lungcan.2018.11.014
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发表时间：
2018-12-01
期刊：
影响因子：
5.3
通讯作者：
Goto, Koichi
中科院分区：
文献类型：
--
作者：
Udagawa, Hibiki;Umemura, Shigeki;Goto, Koichi
目的：小细胞肺癌（SCLC）的全面基因组分析揭示了各种遗传改变。然而，在晚期小细胞肺癌中，很难获得合适的样本进行遗传分析。因此，遗传改变对小细胞肺癌患者预后的影响尚未得到很好的研究。因此，本研究评估了遗传变异对小细胞肺癌patients.Materials和方法生存的影响：我们收集了220例晚期小细胞肺癌患者癌症治疗前获得的样本。从样本中提取的基因组DNA经过1.499 Mb大小的定制面板，该面板捕获244个癌症相关基因的所有外显子，并通过下一代测序分析捕获的DNA。结果：204例（93%）样本的基因分析是成功的。在14例（7%）、150例（74%）和85例（42%）肿瘤中检测到PI 3 K/AKT/mTOR通路的遗传改变和TP 53和RB 1的失活突变。在广泛性疾病（艾德，N = 126）患者中，多变量分析显示，PI 3 K/AKT/mTOR通路中存在遗传改变与不利的生存率显著相关[风险比（HR），2.14; 95% CI 1.02-4.06; P = 0.04]。在有限的疾病（LD，N = 78）患者中，TP 53突变的存在和RB 1突变的缺失与不利的生存率显着相关（HR，2.41; 95% CI 1.21-5.34; P = 0.01，HR，0.45; 95% CI 0.25-0.79; P < 0.01）。基于测序的基因谱分析是可行的，并有助于预测晚期SCLC的预后。PI 3 K/AKT/mTOR通路的遗传改变、TP 53突变和RB 1突变与SCLC患者的预后相关。ED-SCLC和LD-SCLC与预后相关的遗传变异不同。
Objectives: Comprehensive genomic analysis of small-cell lung cancer (SCLC) revealed various genetic alterations. However, obtaining suitable samples for genetic analysis is difficult in advanced SCLC. Thus, the prognostic effect of genetic alterations on the outcome of SCLC patients has not been well investigated. Therefore, this study evaluated the effect of genetic alterations on the survival of SCLC patients.Materials and methods: We collected samples obtained from 220 patients with advanced SCLC before cancer treatment. Genomic DNA extracted from the samples was subjected to a 1.499 Mb-sized custom panel that captured all exons of 244 cancer-related genes, and the captured DNA was analyzed through next-generation sequencing. The associations between genetic alterations and overall survival were evaluated.Results: Genetic analysis was successful in 204 samples (93%). Genetic alterations in the PI3K/AKT/mTOR pathway and inactivating mutations in TP53 and RB1 were detected in 14 (7%), 150 (74%), and 85 (42%) of the tumors. In extensive disease (ED, N = 126) patients, multivariate analysis revealed that the presence of genetic alterations in the PI3K/AKT/mTOR pathway was significantly associated with unfavorable survival [hazard ratio (HR), 2.14; 95% CI 1.02-4.06; P = 0.04]. In limited disease (LD, N = 78) patients, the presence of TP53 mutation and the absence of RB1 mutation were significantly associated with unfavorable survival (HR, 2.41; 95% CI 1.21-5.34; P = 0.01, and HR, 0.45; 95% CI 0.25-0.79; P < 0.01, respectively).Conclusions: Sequencing-based genetic profiling is feasible and useful to predict the prognosis in advanced SCLC. Genetic alterations in the PI3K/AKT/mTOR pathway, TP53 mutations and RB1 mutations were associated with prognosis in SCLC patients. The genetic alterations associated with the prognosis were different between ED-SCLC and LD-SCLC.