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. 2020 Jul 20;30(11):1024–1042. doi: 10.1038/s41422-020-0374-x

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© Center for Excellence in Molecular Cell Science, CAS 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a t-SNE plot of 7581 malignant cells from 11 patients (indicated by colors) reveals tumor-specific clusters. b A heatmap shows genes (rows) that are differentially expressed across 11 individual primary tumors (columns). Red: high expression; blue: low expression. Selected genes are highlighted. c A heatmap depicts the pairwise correlations of 44 metagenes derived from 11 tumors. Clustering identified five coherent malignant gene expression signatures across the tumors. d Each panel (from top to bottom) shows violin plots that depict the scores for one of the five malignant signatures for malignant cells from the 11 tumors. e Changes in gene expression for the five malignant signatures in response to different EBV infection statuses (95 positive vs 14 negative, detected by in situ hydridization with the EBV-encoded small RNAs) in NPC Cohort A are shown (P values were based on the Wilcoxon rank-sum test). The box plot center corresponds to the median, with the box and whiskers corresponding to the interquartile range and 1.5× interquartile range, respectively. f A bar plot shows the direction and statistical significance (P values were based on the Spearman correlation test) of the associations between each of the malignant signatures and stromal/intratumoral TILs in NPC Cohort A. g Kaplan–Meier curves for progression-free survival in the 88 patients in NPC Cohort A stratified according to high vs low expression of the cell cycling signature. Cox regression HR and 95% CI obtained after correcting for age, sex, smoking history and disease stage are shown; the corresponding Cox regression P value is also shown. h Prognostic values of the malignant signatures in the 88 patients in NPC Cohort A. Forest plots show HRs (blue/red squares) and CIs (horizontal ranges) derived from Cox regression survival analyses for progression-free survival in multivariable analyses adjusted for age, sex, smoking history and disease stage; the corresponding Cox regression P values are also shown. Significant results are indicated with red squares.