Universität zu Köln

Stahl, David, Knoll, Rainer ORCID: 0000-0001-8320-5885, Gentles, Andrew J., Vokuhl, Christian, Buness, Andreas and Gutgemann, Ines (2021). Prognostic Gene Expression, Stemness and Immune Microenvironment in Pediatric Tumors. Cancers, 13 (4). BASEL: MDPI. ISSN 2072-6694

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Abstract

Simple Summary Tumors in children and young adults are rare and diagnostically distinct from those occurring in older patients. They frequently arise from developing cells, resembling stem cells, which may explain some of the clinical and biologic differences observed. The aim of this retrospective transcriptome study was to investigate the prognostic landscape, immune tumor microenvironment (TME) and stemness in a cohort of 4068 transcriptomes of such tumors. We find that patients' prognosis correlates with distinct gene expression patterns similar to adult tumor types. Stemness defined by a computational stemness score (mRNAsi) correlates with clinical and molecular parameters that is distinct for each tumor type. In Wilms tumors that recapitulate normal kidney development microscopically, stemness correlates with distinct patterns of immune cell infiltration by transcriptome analysis and by cell localization in tumor tissue. Pediatric tumors frequently arise from embryonal cells, often displaying a stem cell-like (small round blue) morphology in tissue sections. Because recently stemness has been associated with a poor immune response in tumors, we investigated the association of prognostic gene expression, stemness and the immune microenvironment systematically using transcriptomes of 4068 tumors occurring mostly at the pediatric and young adult age. While the prognostic landscape of gene expression (PRECOG) and infiltrating immune cell types (CIBERSORT) is similar to that of tumor entities occurring mainly in adults, the patterns are distinct for each diagnostic entity. A high stemness score (mRNAsi) correlates with clinical and morphologic subtype in Wilms tumors, neuroblastomas, synovial sarcomas, atypical teratoid rhabdoid tumors and germ cell tumors. In neuroblastomas, a high mRNAsi is associated with shortened overall survival. In Wilms tumors a high mRNAsi correlates with blastemal morphology, whereas tumors with predominant epithelial or stromal differentiation have a low mRNAsi and a high percentage of M2 type macrophages. This could be validated in Wilms tumor tissue (n = 78). Here, blastemal areas are low in M2 macrophage infiltrates, while nearby stromal differentiated areas contain abundant M2 macrophages, suggesting local microanatomic regulation of the immune response.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Stahl, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Knoll, Rainer UNSPECIFIED orcid.org/0000-0001-8320-5885 UNSPECIFIED Gentles, Andrew J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vokuhl, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Buness, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Gutgemann, Ines UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-582821
DOI:	10.3390/cancers13040854
Journal or Publication Title:	Cancers
Volume:	13
Number:	4
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58282