TY - JOUR T1 - Patient-derived non-small cell lung cancer xenograft mirrors complex tumor heterogeneity JF - Cancer Biology and Medicine JO - Cancer Biol Med SP - 184 LP - 198 DO - 10.20892/j.issn.2095-3941.2020.0012 VL - 18 IS - 1 AU - Xuanming Chen AU - Cheng Shen AU - Zhe Wei AU - Rui Zhang AU - Yongsheng Wang AU - Lili Jiang AU - Ke Chen AU - Shuang Qiu AU - Yuanli Zhang AU - Ting Zhang AU - Bin Chen AU - Yanjun Xu AU - Qiyi Feng AU - Jinxing Huang AU - Zhihui Zhong AU - Hongxia Li AU - Guowei Che AU - Kai Xiao Y1 - 2021/02/01 UR - http://www.cancerbiomed.org/content/18/1/184.abstract N2 - 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. ER -