Prognostic value of circulating tumor DNA using target next-generation sequencing in extensive-stage small-cell lung cancer
Prognostic value of circulating tumor DNA using target next-generation sequencing in extensive-stage small-cell lung cancer
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DOI：
10.1016/j.lungcan.2023.01.015
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发表时间：
2023-02-07
期刊：
影响因子：
5.3
通讯作者：
Guo，Linlang
中科院分区：
文献类型：
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作者：
Zhang，Jiexia;Zhou，Ningning;Guo，Linlang
背景化疗仍是小细胞肺癌(SCLC)的主要治疗手段。液体活检为监测SCLC患者的疾病进展提供了一种方便和非侵入性的检测方法。方法我们对69例广泛期(ES)-SCLC患者的159份血浆样本进行了下一代测序。循环肿瘤(CT)DNA水平以每毫升单倍体基因组当量(HGE/毫升)为单位进行量化。MuTect2用于检测单核苷酸变异和短插入/缺失。结果在我们的队列中，69份诊断时的血浆样本中有66份(95.7%)有可检测到的体细胞突变，其中TP53(%)和RB1(56%)是最常见的突变，以及一些常见的小细胞肺癌相关基因的拷贝数变异。与单独组织检测相比，ctDNA和组织检测相结合的方法将可操作突变的总体检测率从19.4%提高到26.9%。此外，ctDNA水平在治疗过程中动态变化，并与无进展生存率的降低显著相关。值得注意的是，在诊断时和疾病进展过程中都检测到了可操作的突变。结论我们的研究通过连续的ctDNA检测揭示了动态的体细胞突变情况，并证实了ctDNA水平可以反映肿瘤负担并预测广泛分期的小细胞肺癌患者的预后。此外，我们还证明，血浆ctDNA分析可以为小细胞肺癌的潜在靶向治疗提供体细胞突变的实时信息。
BackgroundChemotherapy remains the mainstay of treatment for small-cell lung cancer (SCLC). Liquid biopsies provide a convenient and non-invasive detection method for monitoring disease progression in patients with SCLC.MethodsWe performed next-generation sequencing of 159 plasma samples from 69 patients with extensive-stage (ES)-SCLC. Circulating tumor (ct)DNA levels were quantified in haploid genome equivalents per mL (hGE/mL). MuTect2 was used to detect single nucleotide variants and short insertions/deletions. The “enrichKEGG” function in the “clusterProfiler” R package was used to enrich the mutated genes that only appeared during disease progression.ResultsIn our cohort, 66 of 69 (95.7%) plasma samples at the time of diagnosis had detectable somatic mutations; TP53 (89%) and RB1(56%) were the most frequent mutations, as well as copy number variations in some common SCLC-related genes such as RB1. Combination ctDNA and tissue testing improved the overall detection rate of actionable mutations from 19.4% to 26.9% compared with that of tissue detection alone. In addition, ctDNA levels changed dynamically during the course of treatment and were significantly associated with decreased progression-free survival. Notably, actionable mutations were detected at the time of diagnosis and during disease progression.ConclusionsOur study revealed a dynamic somatic mutation profile through continuous ctDNA detection and confirmed that ctDNA levels can reflect tumor burden and predict PFS in patients with extensive stage-SCLC. Furthermore, we demonstrated that plasma ctDNA assays can provide real-time information on somatic mutations for potential targeted therapies for SCLC.