Patient-derived xenograft model engraftment predicts poor prognosis after surgery in patients with pancreatic cancer
Patient-derived xenograft model engraftment predicts poor prognosis after surgery in patients with pancreatic cancer
复制标题
患者来源的异种移植模型植入预测胰腺癌患者术后预后不良
DOI：
10.1016/j.pan.2020.02.008
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发表时间：
2020-04-01
期刊：
影响因子：
3.6
通讯作者：
Liang, Tingbo
中科院分区：
文献类型：
--
作者：
Chen, Qi;Wei, Tao;Liang, Tingbo
目的：利用从胰腺癌（PC）患者切除的肿瘤在裸鼠中建立第一代患者来源的异种移植（PDX）模型并进行评估，以确定影响异种移植成功的关键因素并预测患者预后。
方法：将2016年5月至2018年4月在我院接受根治性切除术的PC患者的原发性肿瘤样本异种移植到裸鼠体内。对肿瘤大小进行2个月的评估。分析患者的基线特征和随访数据。
结果：从67例患者中建立了肿瘤异种移植模型；30例（44.8%）成功，37例（55.2%）失败。异种移植模型能够重现原发性肿瘤的病理和遗传信息。单因素分析确定肿瘤植入、术后CA19 - 9、肿瘤大小、淋巴结状态和淋巴管浸润是无病生存期（DFS）的显著预测因素（分别为P = 0.000、0.023、0.004、0.035和0.005）。多因素Cox回归分析证实肿瘤植入、肿瘤大小和淋巴管浸润是DFS的独立危险因素（分别为P = 0.000、0.039和0.025）。肿瘤植入对DFS的风险比为0.239（95%置信区间，0.109 - 0.524）。DFS的Kaplan - Meier分析表明，植入组与植入失败组相比预后不良（6.2个月对12.2个月，对数秩检验P = 0.000）。
结论：原发性PC肿瘤的病理和遗传信息在裸鼠的PDX肿瘤模型中得以重现。此外，植入成功是手术后患者疾病复发的有效预测指标。（C）2020国际胰腺病协会（IAP）和欧洲胰腺病俱乐部（EPC）。由爱思唯尔出版集团出版。
Objectives: To establish and evaluate a first generation patient-derived xenograft (PDX) model in nude mice using tumors resected from pancreatic cancer (PC) patients for the identification of key factors that influence xenograft success and prediction of patient prognosis.Methods: Primary tumor samples harvested from PC patients who underwent curative resection between May 2016 and April 2018 at our hospital were xenografted into nude mice. Tumor size was evaluated for 2 months. Patients' baseline characteristics and follow-up data were analyzed.Results: Tumor xenograft models were generated from 67 patients; 30 (44.8%) were successful and 37 (55.2%) failed. Xenograft models could recapitulate the pathology and genetic information of the primary tumors. Univariate analysis identified tumor engraftment, post-operation CA19-9, tumor size, lymph node status, and lymphovascular invasion as significant predictors (P=0.000, 0.023, 0.004, 0.035 and 0.005, respectively) of disease-free survival (DFS). Multivariate Cox regression analysis confirmed tumor engraftment, tumor size and lymphovascular invasion function as independent risk factors for DFS (P=0.000, 0.039 and 0.025, respectively). The hazard ratio of tumor engraftment for DFS was 0.239 (95% confidence interval, 0.109 to 0.524). Kaplan-Meier analysis of DFS indicated an unfavorable outcome in the engraftment group compared to that in the failed engraftment group (6.2 vs. 12.2 months, log rank P=0.000).Conclusion: The pathology and genetic information of primary PC tumors are recapitulated in the PDX tumor model in nude mice. Furthermore, engraftment success is an effective predictor of disease recurrence in patients after surgery. (C) 2020 IAP and EPC. Published by Elsevier B.V.