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Table S2 from Molecular Profiling Reveals Unique Immune and Metabolic Features of Melanoma Brain Metastases

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posted on 2023-04-03, 22:41 authored by Grant M. Fischer, Ali Jalali, David A. Kircher, Won-Chul Lee, Jennifer L. McQuade, Lauren E. Haydu, Aron Y. Joon, Alexandre Reuben, Mariana P. de Macedo, Fernando C. L. Carapeto, Chendong Yang, Anuj Srivastava, Chandrashekar R. Ambati, Arun Sreekumar, Courtney W. Hudgens, Barbara Knighton, Wanleng Deng, Sherise D. Ferguson, Hussein A. Tawbi, Isabella C. Glitza, Jeffrey E. Gershenwald, Y. N. Vashisht Gopal, Patrick Hwu, Jason T. Huse, Jennifer A. Wargo, P. Andrew Futreal, Nagireddy Putluri, Alexander J. Lazar, Ralph J. DeBerardinis, Joseph R. Marszalek, Jianjun Zhang, Sheri L. Holmen, Michael T. Tetzlaff, Michael A. Davies

Table S2: Differentially Expressed Genes in Patient-Matched Melanoma Brain and Extracranial Metastases. Comprehensive list of the 494 differentially expressed genes (adjusted p<0.05) between 35 MBMs and 42 patient-matched ECMs (from 29 patients). Results acquired via EdgeR-limma-voom R packages. Gene names are listed according to HGNC nomenclature. "Log2FC" is the estimate of the log2-fold-change of the gene in MBMs relative to patient-matched ECMs. "AveExr" is the average log2-expression for the gene across all samples. "t" is the moderated t-statistic. "P.Value" is the nominal p-value. "Adj.P.Val" is the p-value corrected for multiple testing via Benjamini-Hochberg procedure. "B" is the log-odds that the gene is differentially expressed.

Funding

University of Texas MD Anderson

National Center for Advancing Translational Sciences

Dr. Miriam and Sheldon G. Adelson Medical Research Foundation

AIM at Melanoma Foundation

NIH

NCI

Cancer Prevention Research Institute of Texas

CPRIT

Melanoma Research Alliance

Dr. John M. Skibber Professorship of MD Anderson, the Robert and Lynne Grossman Family Foundation, and the Michael and Patricia Booker Melanoma Research Endowment

Anderson Melanom

ACS

Baylor College of Medicine

History

ARTICLE ABSTRACT

There is a critical need to improve our understanding of the pathogenesis of melanoma brain metastases (MBM). Thus, we performed RNA sequencing on 88 resected MBMs and 42 patient-matched extracranial metastases; tumors with sufficient tissue also underwent whole-exome sequencing, T-cell receptor sequencing, and IHC. MBMs demonstrated heterogeneity of immune infiltrates that correlated with prior radiation and post-craniotomy survival. Comparison with patient-matched extracranial metastases identified significant immunosuppression and enrichment of oxidative phosphorylation (OXPHOS) in MBMs. Gene-expression analysis of intracranial and subcutaneous xenografts, and a spontaneous MBM model, confirmed increased OXPHOS gene expression in MBMs, which was also detected by direct metabolite profiling and [U-13C]-glucose tracing in vivo. IACS-010759, an OXPHOS inhibitor currently in early-phase clinical trials, improved survival of mice bearing MAPK inhibitor–resistant intracranial melanoma xenografts and inhibited MBM formation in the spontaneous MBM model. The results provide new insights into the pathogenesis and therapeutic resistance of MBMs. Improving our understanding of the pathogenesis of MBMs will facilitate the rational development and prioritization of new therapeutic strategies. This study reports the most comprehensive molecular profiling of patient-matched MBMs and extracranial metastases to date. The data provide new insights into MBM biology and therapeutic resistance.See related commentary by Egelston and Margolin, p. 581.This article is highlighted in the In This Issue feature, p. 565

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