Transcriptional Profiling Identifies Prognostic Gene Signatures for Conjunctival Extranodal Marginal Zone Lymphoma

This study characterizes the transcriptional profile and the cellular tumor microenvironment of conjunctival extranodal marginal zone lymphoma (EMZL) and identifies prognostically relevant biomarkers. Ten formalin-fixed and paraffin-embedded conjunctival EMZL and eight healthy conjunctival specimens...

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Main Authors: Julian Wolf, Thomas Reinhard, Rozina Ida Hajdu, Günther Schlunck, Claudia Auw-Haedrich, Clemens Lange
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/13/1/115
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author Julian Wolf
Thomas Reinhard
Rozina Ida Hajdu
Günther Schlunck
Claudia Auw-Haedrich
Clemens Lange
author_facet Julian Wolf
Thomas Reinhard
Rozina Ida Hajdu
Günther Schlunck
Claudia Auw-Haedrich
Clemens Lange
author_sort Julian Wolf
collection DOAJ
description This study characterizes the transcriptional profile and the cellular tumor microenvironment of conjunctival extranodal marginal zone lymphoma (EMZL) and identifies prognostically relevant biomarkers. Ten formalin-fixed and paraffin-embedded conjunctival EMZL and eight healthy conjunctival specimens were analyzed by Massive Analysis of cDNA Ends (MACE) RNA sequencing. The 3417 upregulated genes in conjunctival EMZL were involved in processes such as B cell proliferation and Rac protein signaling, whereas the 1188 downregulated genes contributed most significantly to oxidative phosphorylation and UV protection. The tumor microenvironment, as determined by deconvolution analysis, was mainly composed of multiple B cell subtypes which reflects the tumor’s B cell lineage. However, several T cell types, including T helper 2 cells and regulatory T cells, as well as innate immune cell types, such as anti-inflammatory macrophages and plasmacytoid dendritic cells, were also strongly enriched in conjunctival EMZL. A 13-biomarker prognostic panel, including <i>S100A8</i> and <i>S100A9</i>, classified ocular and extraocular tumor recurrence, exceeded prognostic accuracy of Ann Arbor and American Joint Committee on Cancer (AJCC) staging, and demonstrated prognostic value for patient survival in 21 different cancer types in a database of 12,332 tumor patients. These findings may lead to new options of targeted therapy and may improve prognostic prediction for conjunctival EMZL.
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spelling doaj.art-b124c53377f044bfbfbbfa5aa47cf0252023-11-30T21:22:59ZengMDPI AGBiomolecules2218-273X2023-01-0113111510.3390/biom13010115Transcriptional Profiling Identifies Prognostic Gene Signatures for Conjunctival Extranodal Marginal Zone LymphomaJulian Wolf0Thomas Reinhard1Rozina Ida Hajdu2Günther Schlunck3Claudia Auw-Haedrich4Clemens Lange5Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyEye Center, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyEye Center, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyEye Center, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyEye Center, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyOphtha-Lab, Department of Ophthalmology, St. Franziskus Hospital, 48145 Münster, GermanyThis study characterizes the transcriptional profile and the cellular tumor microenvironment of conjunctival extranodal marginal zone lymphoma (EMZL) and identifies prognostically relevant biomarkers. Ten formalin-fixed and paraffin-embedded conjunctival EMZL and eight healthy conjunctival specimens were analyzed by Massive Analysis of cDNA Ends (MACE) RNA sequencing. The 3417 upregulated genes in conjunctival EMZL were involved in processes such as B cell proliferation and Rac protein signaling, whereas the 1188 downregulated genes contributed most significantly to oxidative phosphorylation and UV protection. The tumor microenvironment, as determined by deconvolution analysis, was mainly composed of multiple B cell subtypes which reflects the tumor’s B cell lineage. However, several T cell types, including T helper 2 cells and regulatory T cells, as well as innate immune cell types, such as anti-inflammatory macrophages and plasmacytoid dendritic cells, were also strongly enriched in conjunctival EMZL. A 13-biomarker prognostic panel, including <i>S100A8</i> and <i>S100A9</i>, classified ocular and extraocular tumor recurrence, exceeded prognostic accuracy of Ann Arbor and American Joint Committee on Cancer (AJCC) staging, and demonstrated prognostic value for patient survival in 21 different cancer types in a database of 12,332 tumor patients. These findings may lead to new options of targeted therapy and may improve prognostic prediction for conjunctival EMZL.https://www.mdpi.com/2218-273X/13/1/115conjunctival lymphomaEMZLprognosisrecurrencecellular tumor microenvironmentRNA sequencing
spellingShingle Julian Wolf
Thomas Reinhard
Rozina Ida Hajdu
Günther Schlunck
Claudia Auw-Haedrich
Clemens Lange
Transcriptional Profiling Identifies Prognostic Gene Signatures for Conjunctival Extranodal Marginal Zone Lymphoma
Biomolecules
conjunctival lymphoma
EMZL
prognosis
recurrence
cellular tumor microenvironment
RNA sequencing
title Transcriptional Profiling Identifies Prognostic Gene Signatures for Conjunctival Extranodal Marginal Zone Lymphoma
title_full Transcriptional Profiling Identifies Prognostic Gene Signatures for Conjunctival Extranodal Marginal Zone Lymphoma
title_fullStr Transcriptional Profiling Identifies Prognostic Gene Signatures for Conjunctival Extranodal Marginal Zone Lymphoma
title_full_unstemmed Transcriptional Profiling Identifies Prognostic Gene Signatures for Conjunctival Extranodal Marginal Zone Lymphoma
title_short Transcriptional Profiling Identifies Prognostic Gene Signatures for Conjunctival Extranodal Marginal Zone Lymphoma
title_sort transcriptional profiling identifies prognostic gene signatures for conjunctival extranodal marginal zone lymphoma
topic conjunctival lymphoma
EMZL
prognosis
recurrence
cellular tumor microenvironment
RNA sequencing
url https://www.mdpi.com/2218-273X/13/1/115
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AT rozinaidahajdu transcriptionalprofilingidentifiesprognosticgenesignaturesforconjunctivalextranodalmarginalzonelymphoma
AT guntherschlunck transcriptionalprofilingidentifiesprognosticgenesignaturesforconjunctivalextranodalmarginalzonelymphoma
AT claudiaauwhaedrich transcriptionalprofilingidentifiesprognosticgenesignaturesforconjunctivalextranodalmarginalzonelymphoma
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