The vascular landscape of human cancer
Benjamin M. Kahn, Alfredo Lucas, Rohan G. Alur, Maximillian D. Wengyn, Gregory W. Schwartz, Jinyang Li, Kathryn Sun, H. Carlo Maurer, Kenneth P. Olive, Robert B. Faryabi, Ben Z. Stanger
Benjamin M. Kahn, Alfredo Lucas, Rohan G. Alur, Maximillian D. Wengyn, Gregory W. Schwartz, Jinyang Li, Kathryn Sun, H. Carlo Maurer, Kenneth P. Olive, Robert B. Faryabi, Ben Z. Stanger
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Research Article Angiogenesis Oncology

The vascular landscape of human cancer

Abstract

Tumors depend on a blood supply to deliver oxygen and nutrients, making tumor vasculature an attractive anticancer target. However, only a fraction of patients with cancer benefit from angiogenesis inhibitors. Whether antiangiogenic therapy would be more effective if targeted to individuals with specific tumor characteristics is unknown. To better characterize the tumor vascular environment both within and between cancer types, we developed a standardized metric — the endothelial index (EI) — to estimate vascular density in over 10,000 human tumors, corresponding to 31 solid tumor types, from transcriptome data. We then used this index to compare hyper- and hypovascular tumors, enabling the classification of human tumors into 6 vascular microenvironment signatures (VMSs) based on the expression of a panel of 24 vascular “hub” genes. The EI and VMS correlated with known tumor vascular features and were independently associated with prognosis in certain cancer types. Retrospective testing of clinical trial data identified VMS2 classification as a powerful biomarker for response to bevacizumab. Thus, we believe our studies provide an unbiased picture of human tumor vasculature that may enable more precise deployment of antiangiogenesis therapy.

Authors

Benjamin M. Kahn, Alfredo Lucas, Rohan G. Alur, Maximillian D. Wengyn, Gregory W. Schwartz, Jinyang Li, Kathryn Sun, H. Carlo Maurer, Kenneth P. Olive, Robert B. Faryabi, Ben Z. Stanger

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Figure 6

Relationship between the VMS and the EI differs across cancer types.

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Relationship between the VMS and the EI differs across cancer types. (A)...
(A) Violin plots showing EI scores (y axis) of tumors belonging to VMS1–VMS6 (x axis) in 31 individual cancer types. Significant differences in EI score of tumors with different VMSs (within each cancer type) were detected using a Kruskal-Wallis rank-sum test (*P < 0.05, **P < 0.01, ***P < 0.001). Kruskal-Wallis testing was followed by Conover testing of pairwise comparisons to identify specific associations between the VMS and EI score within cancer types. The threshold FDR met by all pairwise comparisons is reported in the text for each VMS-EI score association. (B) Heatmap showing the median EI score (0–1, red, high; blue, low) of each vascular microenvironment within 31 solid tumor types. Tumor types are clustered by similarity with respect to their VMS proportions.