Fig. 2: Intratumoral heterogeneity of neuroendocrine differentiation in patient tumors and model systems. | Nature Communications

Fig. 2: Intratumoral heterogeneity of neuroendocrine differentiation in patient tumors and model systems.

From: Heterogeneity of neuroendocrine transcriptional states in metastatic small cell lung cancers and patient-derived models

Fig. 2

a CIBERSORT analysis25 of the 50-gene signature in 100 tumors grouped by NE subtype (left stacked bar chart). Relative proportion of NE and non-NE cells within each SCNC NE subtype (right box plot) (n = 100 tumors; data are presented as mean ± SEM). Two-tailed Student-t test, ****P = 2.07e-20. b Representative photomicrograph images of H&E-stained small cell cancer of the NE subtype with heterogenous morphological features (observations were repeated independently two times). c Intratumoral proportion of NE cells based on CIBERSORT deconvolution in 84 recurrent and metastatic tumors from the current cohort and previously described cohorts of 81 early-stage tumors30, 32 PDX, 120 CDX22,28 models, and 39 immortalized cell lines33,34. Kruskal–Wallis test followed by Dunn’s multiple comparisons test with BH correction, ****P < 0.0001 (ranging from P = 2.13e-26 to 2.08e-07), *P = 0.023. d CIBERSORT analysis25 of the 50-gene signature in six patient-matched tumor biopsies (T) and xenograft tumors (P). e Proportion of NE cells based on CIBERSORT deconvolution in 6 PDX and corresponding donor patient tumors. Paired t-test, P = 0.048 (f) Box plots showing mRNA levels in NE and non-NE tumors for the four transcription factors. Two-tailed Mann–Whitney U-test, ****P < 0.0001 (ranging from P = 2.53e-09 to 4.56e-05), **P = 0.00103, ns, not significant (n = 72 patients). g Heatmap generated by unsupervised hierarchal clustering of the four transcription factors in 72 patients. Neuroendocrine scores and NE status derived from the 50-gene signature, and the molecular subtypes derived from the clustering and the histology are indicated above the heatmap. h Supervised PCA using the expression of the four transcription factors. Each dot represents a patient colored by the transcriptomic category. All tests are two-tailed. All box plots indicate the inter-quartile range (IQR), the middle line corresponds to the median, and the upper and lower whiskers represent observations within 1.5*IQR (Q3 + 1.5*IQR or Q1 − 1.5*IQR). Abbreviations: NE neuroendocrine differentiation; TMM Trimmed Mean of M-values; FPKM Fragments Per Kilobase of Exon Per Million Fragments Mapped; PCA principal component analysis. PDX patient-delivered xenografts; CDX CTC-derived xenografts.

Back to article page