A proteotranscriptomic approach to dissect the molecular landscape of human retinoblastoma
BackgroundRetinoblastoma is a rare pediatric eye cancer caused by mutations in the RB1 gene, which regulates retinal cell growth. Early detection and treatment are critical for preventing vision loss and improving survival outcomes. This study aimed to perform an integrated proteotranscriptomic char...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-05-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1571702/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849312695631740928 |
|---|---|
| author | Julian Wolf Rozina Ida Hajdu Stefaniya Boneva Ira Godbole Lucas Stürzbecher Claudia Auw-Haedrich Wolf A. Lagrèze Hansjürgen Agostini Thomas Reinhard Stefan Tholen Oliver Schilling Günther Schlunck Bertram Bengsch Clemens Lange |
| author_facet | Julian Wolf Rozina Ida Hajdu Stefaniya Boneva Ira Godbole Lucas Stürzbecher Claudia Auw-Haedrich Wolf A. Lagrèze Hansjürgen Agostini Thomas Reinhard Stefan Tholen Oliver Schilling Günther Schlunck Bertram Bengsch Clemens Lange |
| author_sort | Julian Wolf |
| collection | DOAJ |
| description | BackgroundRetinoblastoma is a rare pediatric eye cancer caused by mutations in the RB1 gene, which regulates retinal cell growth. Early detection and treatment are critical for preventing vision loss and improving survival outcomes. This study aimed to perform an integrated proteotranscriptomic characterization of human retinoblastoma to provide a deeper understanding of disease biology and to identify novel therapeutic targets.MethodsPaired tumor and adjacent retinal tissue samples were dissected from seven eyes. RNA sequencing and liquid chromatography-mass spectrometry were performed on the same samples. The spatially resolved cellular landscape was assessed using Imaging Mass Cytometry (IMC).ResultsThe correlation between RNA and protein level was moderate with variations across different pathways, underscoring the value of an integrated proteotranscriptomic approach. IMC identified more than 67,000 single cells in 11 distinct clusters, including antigen presenting cells, T cells, stroma cells, vascular cells and two clusters of proliferating and CD44/c-Myc positive tumor cells. Antigen presenting cells expressed higher levels of CD68 in retinoblastoma compared to controls. ConclusionsCD44+ and high-c-Myc-expressing tumor cells may represent cancer stem cells with possible involvement in metastasis, warranting further validation. Our multilayered approach could pave the way for enhanced molecular assessments and novel targeted therapies for human retinoblastoma. |
| format | Article |
| id | doaj-art-e797eb81ad1a4e23a999e2e7efbd322d |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-e797eb81ad1a4e23a999e2e7efbd322d2025-08-20T03:53:01ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-05-011510.3389/fonc.2025.15717021571702A proteotranscriptomic approach to dissect the molecular landscape of human retinoblastomaJulian Wolf0Rozina Ida Hajdu1Stefaniya Boneva2Ira Godbole3Lucas Stürzbecher4Claudia Auw-Haedrich5Wolf A. Lagrèze6Hansjürgen Agostini7Thomas Reinhard8Stefan Tholen9Oliver Schilling10Günther Schlunck11Bertram Bengsch12Clemens Lange13Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyEye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyEye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyClinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Disease, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyEye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyEye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyEye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyEye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyEye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyInstitute of Surgical Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyInstitute of Surgical Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyEye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyClinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Disease, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyOphtha-Lab, Department of Ophthalmology, St. Franziskus Hospital, Münster, GermanyBackgroundRetinoblastoma is a rare pediatric eye cancer caused by mutations in the RB1 gene, which regulates retinal cell growth. Early detection and treatment are critical for preventing vision loss and improving survival outcomes. This study aimed to perform an integrated proteotranscriptomic characterization of human retinoblastoma to provide a deeper understanding of disease biology and to identify novel therapeutic targets.MethodsPaired tumor and adjacent retinal tissue samples were dissected from seven eyes. RNA sequencing and liquid chromatography-mass spectrometry were performed on the same samples. The spatially resolved cellular landscape was assessed using Imaging Mass Cytometry (IMC).ResultsThe correlation between RNA and protein level was moderate with variations across different pathways, underscoring the value of an integrated proteotranscriptomic approach. IMC identified more than 67,000 single cells in 11 distinct clusters, including antigen presenting cells, T cells, stroma cells, vascular cells and two clusters of proliferating and CD44/c-Myc positive tumor cells. Antigen presenting cells expressed higher levels of CD68 in retinoblastoma compared to controls. ConclusionsCD44+ and high-c-Myc-expressing tumor cells may represent cancer stem cells with possible involvement in metastasis, warranting further validation. Our multilayered approach could pave the way for enhanced molecular assessments and novel targeted therapies for human retinoblastoma.https://www.frontiersin.org/articles/10.3389/fonc.2025.1571702/fullretinoblastomatranscriptomicsproteomicsIMCproteotranscriptomicstranslational medicine |
| spellingShingle | Julian Wolf Rozina Ida Hajdu Stefaniya Boneva Ira Godbole Lucas Stürzbecher Claudia Auw-Haedrich Wolf A. Lagrèze Hansjürgen Agostini Thomas Reinhard Stefan Tholen Oliver Schilling Günther Schlunck Bertram Bengsch Clemens Lange A proteotranscriptomic approach to dissect the molecular landscape of human retinoblastoma Frontiers in Oncology retinoblastoma transcriptomics proteomics IMC proteotranscriptomics translational medicine |
| title | A proteotranscriptomic approach to dissect the molecular landscape of human retinoblastoma |
| title_full | A proteotranscriptomic approach to dissect the molecular landscape of human retinoblastoma |
| title_fullStr | A proteotranscriptomic approach to dissect the molecular landscape of human retinoblastoma |
| title_full_unstemmed | A proteotranscriptomic approach to dissect the molecular landscape of human retinoblastoma |
| title_short | A proteotranscriptomic approach to dissect the molecular landscape of human retinoblastoma |
| title_sort | proteotranscriptomic approach to dissect the molecular landscape of human retinoblastoma |
| topic | retinoblastoma transcriptomics proteomics IMC proteotranscriptomics translational medicine |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1571702/full |
| work_keys_str_mv | AT julianwolf aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT rozinaidahajdu aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT stefaniyaboneva aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT iragodbole aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT lucassturzbecher aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT claudiaauwhaedrich aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT wolfalagreze aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT hansjurgenagostini aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT thomasreinhard aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT stefantholen aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT oliverschilling aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT guntherschlunck aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT bertrambengsch aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT clemenslange aproteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT julianwolf proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT rozinaidahajdu proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT stefaniyaboneva proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT iragodbole proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT lucassturzbecher proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT claudiaauwhaedrich proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT wolfalagreze proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT hansjurgenagostini proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT thomasreinhard proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT stefantholen proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT oliverschilling proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT guntherschlunck proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT bertrambengsch proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma AT clemenslange proteotranscriptomicapproachtodissectthemolecularlandscapeofhumanretinoblastoma |