RT Journal Article
SR Electronic
T1 Patient-derived non-small cell lung cancer xenograft mirrors complex tumor heterogeneity
JF Cancer Biology and Medicine
JO Cancer Biol Med
FD China Anti-Cancer Association
SP 184
OP 198
DO 10.20892/j.issn.2095-3941.2020.0012
VO 18
IS 1
A1 Chen, Xuanming
A1 Shen, Cheng
A1 Wei, Zhe
A1 Zhang, Rui
A1 Wang, Yongsheng
A1 Jiang, Lili
A1 Chen, Ke
A1 Qiu, Shuang
A1 Zhang, Yuanli
A1 Zhang, Ting
A1 Chen, Bin
A1 Xu, Yanjun
A1 Feng, Qiyi
A1 Huang, Jinxing
A1 Zhong, Zhihui
A1 Li, Hongxia
A1 Che, Guowei
A1 Xiao, Kai
YR 2021
UL http://www.cancerbiomed.org/content/18/1/184.abstract
AB Objective: Patient-derived xenograft (PDX) models have shown great promise in preclinical and translational applications, but their consistency with primary tumors in phenotypic, genetic, and pharmacodynamic heterogeneity has not been well-studied. This study aimed to establish a PDX repository for non-small cell lung cancer (NSCLC) and to further elucidate whether it could preserve the heterogeneity within and between tumors in patients.Methods: A total of 75 surgically resected NSCLC specimens were implanted into immunodeficient NOD/SCID mice. Based on the successful establishment of the NSCLC PDX model, we compared the expressions of vimentin, Ki67, EGFR, and PD-L1 proteins between cancer tissues and PDX models using hematoxylin and eosin staining and immunohistochemical staining. In addition, we detected whole gene expression profiling between primary tumors and PDX generations. We also performed whole exome sequencing (WES) analysis in 17 first generation xenografts to further assess whether PDXs retained the patient heterogeneities. Finally, paclitaxel, cisplatin, doxorubicin, atezolizumab, afatininb, and AZD4547 were used to evaluate the responses of PDX models to the standard-of-care agents.Results: A large collection of serially transplantable PDX models for NSCLC were successfully developed. The histology and pathological immunohistochemistry of PDX xenografts were consistent with the patients’ tumor samples. WES and RNA-seq further confirmed that PDX accurately replicated the molecular heterogeneities of primary tumors. Similar to clinical patients, PDX models responded differentially to the standard-of-care treatment, including chemo-, targeted- and immuno-therapeutics.Conclusions: Our established PDX models of NSCLC faithfully reproduced the molecular, histopathological, and therapeutic characteristics, as well as the corresponding tumor heterogeneities, which provides a clinically relevant platform for drug screening, biomarker discovery, and translational research.