检测 cfDNA 片段组学特征在癌症早期检测不同研究中的泛化能力。
Testing the generalizability of cfDNA fragmentomic features across different studies for cancer early detection.
机构信息
The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Medical School of Nanjing University & Clinical Center Institute of Nanjing University, Nanjing, China.
Department of Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
出版信息
Genomics. 2023 Jul;115(4):110662. doi: 10.1016/j.ygeno.2023.110662. Epub 2023 Jun 1.
cfDNA fragmentomic features have been used in cancer detection models; however, the generalizability of the models needs to be tested. We proposed a type of cfDNA fragmentomic feature named chromosomal arm-level fragment size distribution (ARM-FSD), evaluated and compared its performance and generalizability for lung cancer and pan-cancer detection with existing cfDNA fragmentomic features (as reference) by using cohorts from different institutions. The ARM-FSD lung cancer model outperformed the reference model by ∼10% when being tested by two external cohorts (AUC: 0.97 vs. 0.86; 0.87 vs. 0.76). For pan-cancer detection, the performance of the ARM-FSD based model is consistently higher than the reference (AUC: 0.88 vs. 0.75, 0.98 vs. 0.63) in a pan-cancer and a lung cancer external validation cohort, indicating that ARM-FSD model produces stable performance across multiple cohorts. Our study reveals ARM-FSD based models have a higher generalizability, and highlights the necessity of cross-study validation for predictive model development.
cfDNA 片段组学特征已被用于癌症检测模型中;然而,这些模型的泛化能力需要进行测试。我们提出了一种 cfDNA 片段组学特征,名为染色体臂级片段大小分布(ARM-FSD),通过使用来自不同机构的队列,评估并比较了其在肺癌和泛癌检测中与现有 cfDNA 片段组学特征(作为参考)的性能和泛化能力。ARM-FSD 肺癌模型在两个外部队列的测试中优于参考模型约 10%(AUC:0.97 对 0.86;0.87 对 0.76)。对于泛癌检测,基于 ARM-FSD 的模型的性能在泛癌和肺癌外部验证队列中始终高于参考模型(AUC:0.88 对 0.75,0.98 对 0.63),表明 ARM-FSD 模型在多个队列中产生了稳定的性能。我们的研究表明,基于 ARM-FSD 的模型具有更高的泛化能力,并强调了对预测模型开发进行跨研究验证的必要性。