An extracellular vesicle-related gene expression signature identifies high-risk patients in medulloblastoma

被引：9

作者：

Albert, Thomas K. ^{[1
]}

Interlandi, Marta ^{[1
,2
]}

Sill, Martin ^{[3
,4
]}

Graf, Monika ^{[1
]}

Moreno, Natalia ^{[1
]}

Menck, Kerstin ^{[5
]}

Rohlmann, Astrid ^{[6
]}

Melcher, Viktoria ^{[1
]}

Korbanka, Sonja ^{[1
]}

Hoerste, Gerd Meyer zu ^{[7
]}

Lautwein, Tobias ^{[8
]}

Fruehwald, Michael C. ^{[9
]}

Krebs, Christian F. ^{[10
]}

Holdhof, Doerthe ^{[11
,12
]}

Schoof, Melanie ^{[11
,12
]}

Bleckmann, Annalen ^{[5
]}

Missler, Markus ^{[6
]}

Dugas, Martin ^{[2
]}

Schueller, Ulrich ^{[11
,12
,13
]}

Jaeger, Natalie ^{[3
]}

Pfister, Stefan M. ^{[3
,4
,14
,15
]}

Kerl, Kornelius ^{[1
]}

机构：

[1] Univ Childrens Hosp Munster, Dept Pediat Hematol & Oncol, Albert Schweitzer Campus 1, D-48149 Munster, Germany

[2] Westphalian Wilhelms Univ WWU Munster, Inst Med Informat, Munster, Germany

[3] NCT Heidelberg KiTZ, Hopp Childrens Canc Ctr, Heidelberg, Germany

[4] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany

[5] Univ Hosp Munster UKM, Dept Med A Hematol Oncol & Pneumol, Munster, Germany

[6] WWU Munster, Dept Anat & Mol Neurobiol, Munster, Germany

[7] UKM, Dept Neurol, Munster, Germany

[8] Heinrich Heine Univ Dusseldorf, Biol & Med Res Ctr, Dusseldorf, Germany

[9] Childrens Hosp Augsburg, Swabian Childrens Canc Ctr, Augsburg, Germany

[10] Univ Med Ctr Hamburg Eppendorf, Ctr Internal Med, Med Clin & Polyclin 3, Hamburg, Germany

[11] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany

[12] Res Inst Childrens Canc Ctr, Hamburg, Germany

[13] Univ Med Ctr Hamburg Eppendorf, Inst Neuropathol, Hamburg, Germany

[14] German Canc Consortium DKTK Heidelberg, Heidelberg, Germany

[15] Univ Hosp Heidelberg, Dept Pediat Oncol Hematol & Immunol, Heidelberg, Germany

来源：

NEURO-ONCOLOGY | 2021年 / 23卷 / 04期

关键词：

extracellular vesicle; gene expression signature; medulloblastoma; single-cell RNA sequencing; tumor microenvironment; TUMOR-ASSOCIATED MACROPHAGES; CHILDHOOD MEDULLOBLASTOMA; MOLECULAR SUBGROUPS; CELL; HETEROGENEITY; CLASSIFICATION;

D O I：

10.1093/neuonc/noaa254

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background. Medulloblastoma (MB) is a malignant brain tumor in childhood. It comprises 4 subgroups with different clinical behaviors. The aim of this study was to characterize the transcriptomic landscape of MB, both at the level of individual tumors as well as in large patient cohorts. Methods. We used a combination of single-cell transcriptomics, cell culture models and biophysical methods such as nanoparticle tracking analysis and electron microscopy to investigate intercellular communication in the MB tumor niche. Results. Tumor cells of the sonic hedgehog (SHH)-MB subgroup show a differentiation blockade. These cells undergo extensive metabolic reprogramming.The gene expression profiles of individual tumor cells show a partial convergence with those of tumor-associated glial and immune cells. One possible cause is the transfer of extracellular vesicles (EVs) between cells in the tumor niche. We were able to detect EVs in co-culture models of MB tumor cells and oligodendrocytes. We also identified a gene expression signature, EVS, which shows overlap with the proteome profile of large oncosomes from prostate cancer cells. This signature is also present in MB patient samples. A high EVS expression is one common characteristic of tumors that occur in high-risk patients from different MB subgroups or subtypes. Conclusions. With EVS, our study uncovered a novel gene expression signature that has a high prognostic significance across MB subgroups.

引用

页码：586 / 598

页数：13

共 39 条

[1] Proteomics, Post-translational Modifications, and Integrative Analyses Reveal Molecular Heterogeneity within Medulloblastoma Subgroups [J].

Archer, Tenley C. ;

Ehrenberger, Tobias ;

Mundt, Filip ;

Gold, Maxwell P. ;

Krug, Karsten ;

Mah, Clarence K. ;

Mahoney, Elizabeth L. ;

Daniel, Colin J. ;

LeNail, Alexander ;

Ramamoorthy, Divya ;

Mertins, Philipp ;

Mani, D. R. ;

Zhang, Hailei ;

Gillette, Michael A. ;

Clauser, Karl ;

Noble, Michael ;

Tang, Lauren C. ;

Pierre-Francois, Jessica ;

Silterra, Jacob ;

Jensen, James ;

Tamayo, Pablo ;

Korshunov, Andrey ;

Pfister, Stefan M. ;

Kool, Marcel ;

Northcott, Paul A. ;

Sears, Rosalie C. ;

Lipton, Jonathan O. ;

Carr, Steven A. ;

Mesirov, Jill P. ;

Pomeroy, Scott L. ;

Fraenkel, Ernest .

CANCER CELL, 2018, 34 (03) :396-+

[2]

Barnett SC, 1995, DEVELOPMENT, V121, P3969

[3] Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis [J].

Becker, Annette ;

Thakur, Basant Kumar ;

Weiss, Joshua Mitchell ;

Kim, Han Sang ;

Peinado, Hector ;

Lyden, David .

CANCER CELL, 2016, 30 (06) :836-848

[4] Subgroup-specific immune and stromal microenvironment in medulloblastoma [J].

Bockmayr, Michael ;

Mohme, Malte ;

Klauschen, Frederick ;

Winkler, Beate ;

Budczies, Jan ;

Rutkowski, Stefan ;

Schueller, Ulrich .

ONCOIMMUNOLOGY, 2018, 7 (09)

[5] Integrating single-cell transcriptomic data across different conditions, technologies, and species [J].

Butler, Andrew ;

Hoffman, Paul ;

Smibert, Peter ;

Papalexi, Efthymia ;

Satija, Rahul .

NATURE BIOTECHNOLOGY, 2018, 36 (05) :411-+

[6] A transcriptome database for astrocytes, neurons, and oligodendrocytes: A new resource for understanding brain development and function [J].

Cahoy, John D. ;

Emery, Ben ;

Kaushal, Amit ;

Foo, Lynette C. ;

Zamanian, Jennifer L. ;

Christopherson, Karen S. ;

Xing, Yi ;

Lubischer, Jane L. ;

Krieg, Paul A. ;

Krupenko, Sergey A. ;

Thompson, Wesley J. ;

Barres, Ben A. .

JOURNAL OF NEUROSCIENCE, 2008, 28 (01) :264-278

[7] Intertumoral Heterogeneity within Medulloblastoma Subgroups [J].

Cavalli, Florence M. G. ;

Remke, Marc ;

Rampasek, Ladislav ;

Peacock, John ;

Shih, David J. H. ;

Luu, Betty ;

Garzia, Livia ;

Torchia, Jonathon ;

Nor, Carolina ;

Morrissy, A. Sorana ;

Agnihotri, Sameer ;

Thompson, Yuan Yao ;

Kuzan-Fischer, Claudia M. ;

Farooq, Hamza ;

Isaev, Keren ;

Daniels, Craig ;

Cho, Byung-Kyu ;

Kim, Seung-Ki ;

Wang, Kyu-Chang ;

Lee, Ji Yeoun ;

Grajkowska, Wieslawa A. ;

Perek-Polnik, Marta ;

Vasiljevic, Alexandre ;

Faure-Conter, Cecile ;

Jouvet, Anne ;

Giannini, Caterina ;

Rao, Amulya A. Nageswara ;

Li, Kay Ka Wai ;

Ng, Ho-Keung ;

Eberhart, Charles G. ;

Pollack, Ian F. ;

Hamilton, Ronald L. ;

Gillespie, G. Yancey ;

Olson, James M. ;

Leary, Sarah ;

Weiss, William A. ;

Lach, Boleslaw ;

Chambless, Lola B. ;

Thompson, Reid C. ;

Cooper, Michael K. ;

Vibhakar, Rajeev ;

Hauser, Peter ;

van Veelen, Marie-Lise C. ;

Kros, Johan M. ;

French, Pim J. ;

Ra, Young Shin ;

Kumabe, Toshihiro ;

Lopez-Aguilar, Enrique ;

Zitterbart, Karel ;

Sterba, Jaroslav .

CANCER CELL, 2017, 31 (06) :737-+

[8] Gene expression markers of Tumor Infiltrating Leukocytes [J].

Danaher, Patrick ;

Warren, Sarah ;

Dennis, Lucas ;

D'Amico, Leonard ;

White, Andrew ;

Disis, Mary L. ;

Geller, Melissa A. ;

Odunsi, Kunle ;

Beechem, Joseph ;

Fling, Steven P. .

JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2017, 5

[9] Are molecular subgroups of medulloblastomas really prognostic? [J].

Frappaz, Didier ;

Faure-Conter, Cecile ;

Meyronet, David ;

Levard-Bonneville, Alice ;

Beuriat, Pierre-Aurelien ;

Sunyach, Marie P. ;

Barritault, Marc .

CURRENT OPINION IN NEUROLOGY, 2018, 31 (06) :747-751

[10] Resolving medulloblastoma cellular architecture by single-cell genomics [J].

Hovestadt, Volker ;

Smith, Kyle S. ;

Bihannic, Laure ;

Filbin, Mariella G. ;

Shaw, McKenzie L. ;

Baumgartner, Alicia ;

DeWitt, John C. ;

Groves, Andrew ;

Mayr, Lisa ;

Weisman, Hannah R. ;

Richman, Alyssa R. ;

Shore, Marni E. ;

Goumnerova, Liliana ;

Rosencrance, Celeste ;

Carter, Robert A. ;

Phoenix, Timothy N. ;

Hadley, Jennifer L. ;

Tong, Yiai ;

Houston, Jim ;

Ashmun, Richard A. ;

DeCuypere, Michael ;

Sharma, Tanvi ;

Flasch, Diane ;

Silkov, Antonina ;

Ligon, Keith L. ;

Pomeroy, Scott L. ;

Rivera, Miguel N. ;

Rozenblatt-Rosen, Orit ;

Rusert, Jessica M. ;

Wechsler-Reya, Robert J. ;

Li, Xiao-Nan ;

Peyrl, Andreas ;

Gojo, Johannes ;

Kirchhofer, Dominik ;

Loetsch, Daniela ;

Czech, Thomas ;

Dorfer, Christian ;

Haberler, Christine ;

Geyeregger, Rene ;

Halfmann, Angela ;

Gawad, Charles ;

Easton, John ;

Pfister, Stefan M. ;

Regev, Aviv ;

Gajjar, Amar ;

Orr, Brent A. ;

Slavc, Irene ;

Robinson, Giles W. ;

Bernstein, Bradley E. ;

Suva, Mario L. .

NATURE, 2019, 572 (7767) :74-+

← 1 2 3 4 →