Clinical and pathological predictors of engraftment for patient-derived xenografts in lung adenocarcinoma.
Hiroyuki OgawaTakamasa KogaNhu-An PhamNicholas BernardsAlexander GregorYuki SataShinsuke KitazawaYoshihisa HiraishiTsukasa IshiwataMasato AragakiFumi YokoteAndrew EffatKate KazlovichQuan LiKatrina HuenikenMing LiYoshimasa ManiwaMing-Sound TsaoKazuhiro YasufukuPublished in: Lung cancer (Amsterdam, Netherlands) (2024)
Patient-derived xenografts (PDXs) are increasingly utilized in preclinical drug efficacy studies due to their ability to retain the molecular, histological, and drug response characteristics of patient tumors. This study aimed to investigate the factors influencing the successful engraftment of PDXs. Lung adenocarcinoma PDXs were established using freshly resected tumor tissues obtained through surgery. Radiological data of pulmonary nodules from this PDX cohort were analyzed, categorizing them into solid tumors and tumors with ground-glass opacity (GGO) based on preoperative CT images. Gene mutation status was obtained from next generation sequencing data and MassARRAY panel. A total of 254 resected primary lung adenocarcinomas were utilized for PDX establishment, with successful initial engraftment in 58 cases (22.8 %); stable engraftment defined as at least three serial passages was observed in 43 cases (16.9 %). The stable engraftment rates of PDXs from solid tumors and tumors with GGO were 22.1 % (42 of 190 cases) and 1.6 % (1 of 64 cases), respectively (P < 0.001). Adenocarcinomas with advanced stage, poor differentiation, solid histologic subtype, and KRAS or TP53 gene mutations were associated with stable PDX engraftment. Avoiding tumors with GGO features could enhance the cost-effectiveness of establishing PDX models from early-stage resected lung adenocarcinomas.
Keyphrases
- hematopoietic stem cell
- early stage
- lymph node
- electronic health record
- minimally invasive
- computed tomography
- magnetic resonance imaging
- gene expression
- prognostic factors
- patients undergoing
- squamous cell carcinoma
- emergency department
- case report
- mesenchymal stem cells
- dna methylation
- convolutional neural network
- magnetic resonance
- drug induced
- data analysis
- pet ct
- positron emission tomography
- contrast enhanced
- atrial fibrillation
- percutaneous coronary intervention
- coronary artery bypass
- dual energy
- genome wide
- cell free