The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Australia.
The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Australia.
ESMO Open. 2022 Jun;7(3):100452. doi: 10.1016/j.esmoop.2022.100452. Epub 2022 Mar 23.
The incidence of oesophageal adenocarcinoma (OAC) is rapidly increasing and despite improvements in treatment, the 5-year survival rate remains poor. Prognostic biomarkers that address the genomic heterogeneity in this highly complex disease will aid the development of precision therapeutics and improve patient survival. The aim of this study was to determine whether circulating tumour DNA (ctDNA) has prognostic significance as a biomarker in OAC patients.
We profiled 209 blood and tumour samples from 57 OAC patients. Using a panel of 77 cancer genes, we sequenced ctDNA in plasma samples (n = 127) which were taken at multiple time points before and after therapy. In parallel, we sequenced matched tumour samples from 39 patients using the same gene panel. To assess whether the ctDNA profile reflected the tumour heterogeneity, we sequenced additional multi-region primary tumour samples in 17 patients. In addition, we analysed whole-genome and whole-exome sequencing data from primary tumours for a subset of 18 patients.
Using a tumour-agnostic approach, we found that detectable ctDNA variants in post-treatment plasma samples were associated with worse disease-specific survival. To evaluate whether the ctDNA originated from the primary tumour, we carried out a tumour-informed analysis which confirmed post-treatment ctDNA variants were associated with worse survival. To determine whether ctDNA could be used as a clinical follow-up test, we assessed blood samples from multiple time points before and after treatment, in a subset of patients. Results showed that the variant allele frequency of ctDNA variants increased with disease recurrence.
This study demonstrates that ctDNA variants can be detected in patients with OAC and this has potential clinical utility as a prognostic biomarker for survival.
食管腺癌（OAC）的发病率正在迅速上升，尽管治疗有所改善，但 5 年生存率仍然很差。能够解决这种高度复杂疾病中基因组异质性的预后生物标志物将有助于开发精准治疗方法并提高患者生存率。本研究旨在确定循环肿瘤 DNA（ctDNA）作为 OAC 患者的生物标志物是否具有预后意义。
我们对 57 名 OAC 患者的 209 个血液和肿瘤样本进行了分析。使用 77 个癌症基因的panel，我们对治疗前和治疗后多个时间点采集的 127 份血浆样本中的 ctDNA 进行了测序。同时，我们对 39 名患者的匹配肿瘤样本使用相同的基因 panel 进行了测序。为了评估 ctDNA 图谱是否反映了肿瘤异质性，我们对 17 名患者的额外多区域原发性肿瘤样本进行了测序。此外，我们对 18 名患者的一部分进行了原发性肿瘤的全基因组和全外显子组测序数据分析。
使用肿瘤无偏倚方法，我们发现治疗后血浆样本中可检测到的 ctDNA 变体与较差的疾病特异性生存相关。为了评估 ctDNA 是否来自原发性肿瘤，我们进行了肿瘤知情分析，该分析证实治疗后 ctDNA 变体与较差的生存相关。为了确定 ctDNA 是否可以用作临床随访测试，我们评估了治疗前后多个时间点的患者血液样本。结果表明，ctDNA 变体的等位基因频率随着疾病复发而增加。
本研究表明，OAC 患者中可以检测到 ctDNA 变体，并且作为生存的预后生物标志物具有潜在的临床应用价值。
