Establishing a patient-derived colorectal cancer xenograft model for translational research

被引:0
作者
Guan, Zhonghai [1 ]
Chen, Xiangheng [2 ]
Jiang, Xiaoxia [1 ]
Li, Zhongqi [1 ]
Yu, Xiongfei [1 ]
Jin, Ketao [3 ]
Cao, Jiang [4 ]
Teng, Lisong [1 ]
机构
[1] Zhejiang Univ, Affiliated Hosp 1, Dept Surg Oncol, Coll Med, Hangzhou 310000, Zhejiang, Peoples R China
[2] Cent South Univ, Xiangya Hosp 2, Dept Minimally Invas Surg, Changsha 421001, Hunan, Peoples R China
[3] Zhejiang Univ, Shaoxing Hosp, Shaoxing Peoples Hosp, Dept Gastrointestinal Surg, Shaoxing 312000, Zhejiang, Peoples R China
[4] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Clin Res Ctr, Shaoxing, Zhejiang Sheng, Peoples R China
基金
中国国家自然科学基金;
关键词
Patient-derived xenograft model; colorectal cancer; precision medicine; translational research; TUMOR XENOGRAFTS; CELL-LINES; IDENTIFICATION; RESISTANCE; THERAPY; COLON; PANEL;
D O I
暂无
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Colorectal cancer (CRC) remains to present a high incidence and mortality rate, despite of the advances in current targeted theraputic approaches. Accumulating studies indicates that Patient-derived xenograft (PDX) is an important cancer research tool for more personalized precision medicine. In this study, eighty five CRC tumors derived from Chinese patients were transplanted into BALB/c nude mice for PDX models establishment. Immunohistochemical and molecular investigations (such as, Sanger sequencing, AmpliSeq Cancer Hotspot Panel Version 2 and Proteomics) were performed to verify if the PDX retained both features from the patient. Then, PDX (the first generation) initiation engraftment rate and speed related pathologic and genetic factors were explored. We found that 50 out of 85 (58.5%) CRC tumors successfully engrafted. A high genetic concordance between patient donor tumor and PDX was confirmed by pathologic, genetic, and proteomics investigations. CRC tumor staging, tumor location, somatic mutations were correlated with PDX initiation engraftment rate and speed. In conclusion, we established 50 CRC PDX models with a high histologic and genetic representativeness of the primary tumor. This platform will represent a reliable tool for CRC precision medicine and cancer translational research.
引用
收藏
页码:21346 / +
页数:13
相关论文
共 31 条
[1]  
[Anonymous], SCI TRANSL MED
[2]   Examining the utility of patient-derived xenograft mouse models [J].
Aparicio, Samuel ;
Hidalgo, Manuel ;
Kung, Andrew L. .
NATURE REVIEWS CANCER, 2015, 15 (05) :311-316
[3]   Building the foundation for genomics in precision medicine [J].
Aronson, Samuel J. ;
Rehm, Heidi L. .
NATURE, 2015, 526 (7573) :336-342
[4]   Phase II and Phase III attrition rates 2011-2012 [J].
Arrowsmith, John ;
Miller, Philip .
NATURE REVIEWS DRUG DISCOVERY, 2013, 12 (08) :568-568
[5]   Phase II failures: 2008-2010 [J].
Arrowsmith, John .
NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (05) :1-1
[6]   A Molecularly Annotated Platform of Patient-Derived Xenografts ("Xenopatients") Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer [J].
Bertotti, Andrea ;
Migliardi, Giorgia ;
Galimi, Francesco ;
Sassi, Francesco ;
Torti, Davide ;
Isella, Claudio ;
Cora, Davide ;
Di Nicolantonio, Federica ;
Buscarino, Michela ;
Petti, Consalvo ;
Ribero, Dario ;
Russolillo, Nadia ;
Muratore, Andrea ;
Massucco, Paolo ;
Pisacane, Alberto ;
Molinaro, Luca ;
Valtorta, Emanuele ;
Sartore-Bianchi, Andrea ;
Risio, Mauro ;
Capussotti, Lorenzo ;
Gambacorta, Marcello ;
Siena, Salvatore ;
Medico, Enzo ;
Sapino, Anna ;
Marsoni, Silvia ;
Comoglio, Paolo M. ;
Bardelli, Alberto ;
Trusolino, Livio .
CANCER DISCOVERY, 2011, 1 (06) :508-523
[7]   Colorectal cancer [J].
Brenner, Hermann ;
Kloor, Matthias ;
Pox, Christian Peter .
LANCET, 2014, 383 (9927) :1490-1502
[8]   Establishment of a patient-derived intrahepatic cholangiocarcinoma xenograft model with KRAS mutation [J].
Cavalloni, Giuliana ;
Peraldo-Neia, Caterina ;
Sassi, Francesco ;
Chiorino, Giovanna ;
Sarotto, Ivana ;
Aglietta, Massimo ;
Leone, Francesco .
BMC CANCER, 2016, 16
[9]   Cancer Statistics in China, 2015 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Baade, Peter D. ;
Zhang, Siwei ;
Zeng, Hongmei ;
Bray, Freddie ;
Jemal, Ahmedin ;
Yu, Xue Qin ;
He, Jie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132
[10]   Colorectal cancer patient-derived xenografted tumors maintain characteristic features of the original tumors [J].
Cho, Yong Beom ;
Hong, Hye Kyung ;
Choi, Yoon-La ;
Oh, Ensel ;
Joo, Kyeung Min ;
Jin, Juyoun ;
Nam, Do-Hyun ;
Ko, Young-Hyeh ;
Lee, Woo Yong .
JOURNAL OF SURGICAL RESEARCH, 2014, 187 (02) :502-509