title: Integrated analysis of transcriptome in cancer patient-derived xenografts.
abstract: Patient-derived xenograft (PDX) tumor model is a powerful technology in evaluating anti-cancer drugs and facilitating personalized medicines. Multiple research centers and commercial companies have put huge efforts into building PDX mouse models. However, PDX models have not been widely available and their molecular features have not been systematically characterized. In this study, we provided a comprehensive survey of PDX transcriptome by integrating analysis of 58 patients involving 8 different tumors. The median correlation coefficient between patients and xenografts is 0.94, which is higher than that between patients and cell line panel or between patients with the same tumor. Major differential gene expressions in PDX occur in the engraftment of human tumor tissue into mice, while gene expressions are relatively stable over passages. 48 genes are frequently differentially expressed in PDX mice of multiple cancers. They are enriched in extracellular matrix and immune response, and some are reported as targets for anticancer drugs. A simulation study showed that expression change between PDX and patient tumor (6%) would result in acceptable change in drug sensitivity (3%). Our findings demonstrate that PDX mice represent the gene-expression and drug-response features of primary tumors effectively, and it is recommended to monitoring the overall expression profiles and drug target genes in clinical application.
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, SIBS, CAS, 320 Yueyang Road, Shanghai, 200031, China; Shanghai Center for Bioinformation Technology, 1278 Keyuan Road, Shanghai, 201203, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Shanghai High School, Shanghai, 200231, China.
authors.forename: Yinjie
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, SIBS, CAS, 320 Yueyang Road, Shanghai, 200031, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Tang
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, SIBS, CAS, 320 Yueyang Road, Shanghai, 200031, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Li
authors.affiliation: Shanghai Center for Bioinformation Technology, 1278 Keyuan Road, Shanghai, 201203, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shanghai Center for Bioinformation Technology, 1278 Keyuan Road, Shanghai, 201203, China.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, SIBS, CAS, 320 Yueyang Road, Shanghai, 200031, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Ding
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, SIBS, CAS, 320 Yueyang Road, Shanghai, 200031, China; Shanghai Center for Bioinformation Technology, 1278 Keyuan Road, Shanghai, 201203, China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D057285:Precision Medicine; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents