ffee4a5b5f76a8b6233c0fb8a9cba424 302805.pdf 07c8e1c424eca38a115fd7a30ba78b3a16933694 302805.pdf 930ea832b45e34fb63745194eb2194f0a50b236d57f7a260cc9c0ee086aaacc1 302805.pdf Title: Gal-1 Expression Analysis in the GLIOCAT MulticenterStudy: Role as a Prognostic Factor and anImmune-Suppressive Biomarker Subject: Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population. The -galactoside binding protein Galectin-1 (Gal-1) is a protein with a wide range of pro-tumor functions such as proliferation, invasion, angiogenesis, and immune suppression. Here, we evaluated Gal-1 expression by immunohistochemistry in a homogenously treated cohort of GBM (the GLIOCAT project) and correlated its expression with clinical and molecular data. We observed that Gal-1 is a negative prognostic factor in GBM. Interestingly, we observed higher levels of Gal-1 expression in the mesenchymal/classical subtypes compared to the less aggressive proneural subtype. We also observed a Gal-1 expression correlation with immune suppressive signatures of CD4 T-cells and macrophages, as well as with several GBM established biomarkers, including SHC1, PD-L1, PAX2, MEOX2, YKL-40, TCIRG1, YWHAG, OLIG2, SOX2, Ki-67, and SOX11. Moreover, Gal-1 levels were significantly lower in grade 4 IDH-1 mutant astrocytomas, which have a better prognosis. Our results confirm the role of Gal-1 as a prognostic factor and also suggest its value as an immune-suppressive biomarker in GBM. Keywords: Galectin-1; glioblastoma; prognostic factor; IDH-1; mesenchymal molecular subtype; immune-suppression Author: Neus Martínez-Bosch, Noelia Vilariño, Francesc Alameda, Sergi Mojal, Montserrat Arumí-Uria, Cristina Carrato, Iban Aldecoa, Teresa Ribalta, Noemí Vidal, Beatriz Bellosillo, Silvia Menéndez, Sonia Del Barco, Oscar Gallego, Estela Pineda, Raquel López-Martos, Ainhoa Hernández, Carlos Mesia, Anna Esteve-Codina, Nuria de la Iglesia, Carme Balañá, María Martínez-García and Pilar Navarro Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Mar 9 07:31:29 2023 CET ModDate: Thu Mar 9 07:34:56 2023 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3078770 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- 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LHFDNG+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 372 0 LHFDNH+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 375 0 LHFDNI+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 378 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-11-14 02:54:03 CET RepresentationInformation: 302805.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-11-13 14:05:31 CET Size: 3078770 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 604 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Patients Destination: subsection.2.1 Item: Title: Ethical Details Destination: subsection.2.2 Item: Title: Tissue Microarray Preparation Destination: subsection.2.3 Item: Title: Immunohistochemistry Analysis Destination: subsection.2.4 Item: Title: RNA Sequencing and GBM Molecular Subtypes Destination: subsection.2.5 Item: Title: Cell-Type Deconvolution Destination: subsection.2.6 Item: Title: Statistical Analysis Destination: subsection.2.7 Item: Title: Results Destination: section.3 Children: Item: Title: Gal-1 Has Prognostic Value in GBM Destination: subsection.3.1 Item: Title: Correlation between Gal-1 and Clinical or Molecular Data Destination: subsection.3.2 Item: Title: Correlation between Gal-1 and GBM Molecular Subtypes Destination: subsection.3.3 Item: Title: Correlation between Gal-1 Expression and Markers of Inflammation Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Gal-1 Expression Analysis in the GLIOCAT MulticenterStudy: Role as a Prognostic Factor and anImmune-Suppressive Biomarker Author: Neus Martínez-Bosch, Noelia Vilariño, Francesc Alameda, Sergi Mojal, Montserrat Arumí-Uria, Cristina Carrato, Iban Aldecoa, Teresa Ribalta, Noemí Vidal, Beatriz Bellosillo, Silvia Menéndez, Sonia Del Barco, Oscar Gallego, Estela Pineda, Raquel López-Martos, Ainhoa Hernández, Carlos Mesia, Anna Esteve-Codina, Nuria de la Iglesia, Carme Balañá, María Martínez-García and Pilar Navarro Subject: Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population. The -galactoside binding protein Galectin-1 (Gal-1) is a protein with a wide range of pro-tumor functions such as proliferation, invasion, angiogenesis, and immune suppression. Here, we evaluated Gal-1 expression by immunohistochemistry in a homogenously treated cohort of GBM (the GLIOCAT project) and correlated its expression with clinical and molecular data. We observed that Gal-1 is a negative prognostic factor in GBM. Interestingly, we observed higher levels of Gal-1 expression in the mesenchymal/classical subtypes compared to the less aggressive proneural subtype. We also observed a Gal-1 expression correlation with immune suppressive signatures of CD4 T-cells and macrophages, as well as with several GBM established biomarkers, including SHC1, PD-L1, PAX2, MEOX2, YKL-40, TCIRG1, YWHAG, OLIG2, SOX2, Ki-67, and SOX11. Moreover, Gal-1 levels were significantly lower in grade 4 IDH-1 mutant astrocytomas, which have a better prognosis. Our results confirm the role of Gal-1 as a prognostic factor and also suggest its value as an immune-suppressive biomarker in GBM. 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