肺腺癌中患者来源的异种移植物植入的临床和病理预测因子。
Clinical and pathological predictors of engraftment for patient-derived xenografts in lung adenocarcinoma.
发表日期:2024 Jun 28
作者:
Hiroyuki Ogawa, Takamasa Koga, Nhu-An Pham, Nicholas Bernards, Alexander Gregor, Yuki Sata, Shinsuke Kitazawa, Yoshihisa Hiraishi, Tsukasa Ishiwata, Masato Aragaki, Fumi Yokote, Andrew Effat, Kate Kazlovich, Quan Li, Katrina Hueniken, Ming Li, Yoshimasa Maniwa, Ming-Sound Tsao, Kazuhiro Yasufuku
来源:
LUNG CANCER
摘要:
患者来源的异种移植物(PDX)由于能够保留患者肿瘤的分子、组织学和药物反应特征,因此越来越多地用于临床前药物疗效研究。本研究旨在探讨影响PDX成功植入的因素。使用通过手术获得的新鲜切除的肿瘤组织建立肺腺癌 PDX。我们分析了该 PDX 队列中肺结节的放射学数据,并根据术前 CT 图像将其分为实体瘤和磨玻璃样混浊 (GGO) 肿瘤。基因突变状态通过下一代测序数据和 MassARRAY panel 获得。总共 254 例切除的原发性肺腺癌用于 PDX 建立,其中 58 例(22.8%)首次移植成功;在 43 例 (16.9%) 病例中观察到稳定植入,定义为至少连续传代 3 次。实体瘤和 GGO 肿瘤的 PDX 稳定植入率分别为 22.1%(190 例中的 42 例)和 1.6%(64 例中的 1 例)(P < 0.001)。晚期、分化差、实体组织学亚型和 KRAS 或 TP53 基因突变的腺癌与稳定的 PDX 植入相关。避免具有 GGO 特征的肿瘤可以提高从早期切除肺腺癌建立 PDX 模型的成本效益。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。
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.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.