Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Pathology, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abdom Radiol (NY). 2019 Sep;44(9):3148-3157. doi: 10.1007/s00261-019-02112-1.
The aim of this study was to investigate the relationship between CT imaging phenotypes and genetic and biological characteristics in pancreatic ductal adenocarcinoma (PDAC).
In this retrospective study, consecutive patients between April 2015 and June 2016 who underwent PDAC resection were included if previously consented to a targeted sequencing protocol. Mutation status of known PDAC driver genes (KRAS, TP53, CDKN2A, and SMAD4) in the primary tumor was determined by targeted DNA sequencing and results were validated by immunohistochemistry (IHC). Radiomic features of the tumor were extracted from the preoperative CT scan and used to predict genotype and stromal content.
The cohort for analysis consisted of 35 patients. Genomic and IHC analysis revealed alterations in KRAS in 34 (97%) patients, and changes in expression of CDKN2A in 29 (83%), SMAD4 in 16 (46%), and in TP53 in 29 (83%) patients. Models created from radiomic features demonstrated associations with SMAD4 status and the number of genes altered. The number of genes altered was the only significant predictor of overall survival (p = 0.016). By linear regression analysis, a prediction model for stromal content achieved an R value of 0.731 with a root mean square error of 19.5.
In this study, we demonstrate that in PDAC SMAD4 status and tumor stromal content can be predicted using radiomic analysis of preoperative CT imaging. These data show an association between resectable PDAC imaging features and underlying tumor biology and their potential for future precision medicine.
本研究旨在探讨胰腺导管腺癌(PDAC)的 CT 成像表型与遗传和生物学特征之间的关系。
在这项回顾性研究中,纳入了 2015 年 4 月至 2016 年 6 月期间接受 PDAC 切除术且之前同意进行靶向测序方案的连续患者。通过靶向 DNA 测序确定原发肿瘤中已知 PDAC 驱动基因(KRAS、TP53、CDKN2A 和 SMAD4)的突变状态,并通过免疫组织化学(IHC)验证结果。从术前 CT 扫描中提取肿瘤的放射组学特征,并用于预测基因型和基质含量。
用于分析的队列包括 35 名患者。基因组和 IHC 分析显示,34 名(97%)患者的 KRAS 发生改变,29 名(83%)患者的 CDKN2A 表达改变,16 名(46%)患者的 SMAD4 改变,29 名(83%)患者的 TP53 改变。从放射组学特征创建的模型显示与 SMAD4 状态和改变的基因数量相关。改变的基因数量是总生存期的唯一显著预测因素(p=0.016)。通过线性回归分析,基质含量的预测模型的 R 值为 0.731,均方根误差为 19.5。
在这项研究中,我们证明了在 PDAC 中,SMAD4 状态和肿瘤基质含量可以通过术前 CT 成像的放射组学分析来预测。这些数据显示了可切除 PDAC 成像特征与潜在肿瘤生物学之间的关联及其在未来精准医学中的潜力。