Patient-derived non-small cell lung cancer xenograft mirrors complex tumor heterogeneity

Disease-free survival (A) and overall survival (B) of non-small cell lung cancer patients according to the engraftment status of their patient-derived tumor xenografts using Kaplan-Meier plots and the log-rank test.

Histopathological characterization of patient primary tumors and corresponding xenografts. (A) Representative immunohistochemical staining for TTF1 and P40. (B) Representative hematoxylin and eosin staining and immunohistochemical staining for vimentin, Ki-67, and EGFR of LC-00507. (C) Immunohistochemical staining for PD-L1 of LC-00536 and LC-00781 (400×).

Gene expression analysis between primary patient tumors and patient-derived xenographs (PDXs). (A) Comparison of genome-wide gene expression profiles between matched patient primary non-small cell lung cancer (NSCLC) tumor (patient LC-00666), the corresponding passage 0 (P0) and passage 2 (P2) of xenografts (i, ii, iii). Percent of differentially expressed genes in 3 PDX matched groups (LC-00666, LC-00592, and LC-00368) (iv). (B) Heat map of cancer-related gene expressions in 3 PDX matched groups. The dendrogram shows unsupervised hierarchical clustering of samples according to gene expression patterns. (C) Gene level expression (FPKM) values for the top 50 oncogenes related to NSCLC, and (D) Another 32 differentially expressed oncogenes are presented by the heat map (green = lower than the median, red = greater than the median). (E) Comparison of genome-wide gene expression profiles and (F) NSCLC-related gene expression (FPKM) values between three pieces of intratumoral tissues from one PDX (P4 of LC-00536).

Whole genome sequencing of P0 xenografts from 17 patient-derived xenograph models. (A) Single nucleotide variants (SNV), insertions (Ins) and deletions (Dels) mutations in the exon genome. The type of alteration is indicated by different colors, and bar length represents the number of SNV and Ins/Dels (i, ii). The mutation status (amino acid changes) is shown for a panel of genes that are currently of interest in routine practice for non-small cell lung cancers (iii). (B) Gene copy numbers are presented in a heat map, and variants indicated as gains (i.e., > 2) are shown by shades of green ( = 3), pink ( = 4), and red (> 5).