af8790bd9c30c3b11ba5b1d43c71acef 302111.pdf 50f23dbf8cda7d17370bc267395f0fd7ab25788b 302111.pdf 6c9910f329d50e0d293604b53bc537f486d7ada64d91767ae2753b0eee15d150 302111.pdf Title: CSDE1 Intracellular Distribution as a Biomarker of Melanoma Prognosis Subject: RNA-binding proteins are emerging as critical modulators of oncogenic cell transformation, malignancy and therapy resistance. We have previously found that the RNA-binding protein Cold Shock Domain containing protein E1 (CSDE1) promotes invasion and metastasis of melanoma, the deadliest form of skin cancer and also a highly heterogeneous disease in need of predictive biomarkers and druggable targets. Here, we design a monoclonal antibody useful for IHC in the clinical setting and use it to evaluate the prognosis potential of CSDE1 in an exploratory cohort of 149 whole tissue sections including benign nevi and primary tumors and metastasis from melanoma patients. Contrary to expectations for an oncoprotein, we observed a global decrease in CSDE1 levels with increasing malignancy. However, the CSDE1 cytoplasmic/nuclear ratio exhibited a positive correlation with adverse clinical features of primary tumors and emerged as a robust indicator of progression free survival in cutaneous melanoma, highlighting the potential of CSDE1 as a biomarker of prognosis. Our findings provide a novel feature for prognosis assessment and highlight the intricacies of RNA-binding protein dynamics in cancer progression. Keywords: CSDE1; melanoma; biomarker; RNA-binding protein; cytoplasmic–nuclear ratio; prognosis Author: Alberto Indacochea, Tanit Guitart, Aram Boada, Vicente Peg, Ariadna Quer, Hafid Laayouni, Laura Condal, Pablo Espinosa, Jose Luis Manzano and Fátima Gebauer Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Thu Feb 15 14:12:36 2024 CET ModDate: Thu Feb 15 14:16:15 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2066760 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- AIQCCL+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 DRZUJM+VnURWPalladioL Type 1 Custom yes yes yes 16 0 MPZNWV+URWPalladioL-Bold Type 1 Custom yes yes yes 21 0 KPWWNH+URWPalladioL-Roma Type 1 Custom yes yes yes 27 0 WHZFHY+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 48 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 51 0 URYLRZ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 71 0 TSMJFB+CMSY10 Type 1 Builtin yes yes yes 76 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 92 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 96 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 100 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 104 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 111 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 118 0 ArialMT TrueType WinAnsi no no no 126 0 SymbolMT TrueType WinAnsi no no no 129 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 147 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 151 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 155 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 159 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 166 0 BCDLEE+Arial-BoldMT TrueType WinAnsi yes yes no 174 0 ArialMT TrueType WinAnsi no no no 178 0 OVNEXW+EURM10 Type 1 Builtin yes yes yes 201 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 210 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 214 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 218 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 222 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 229 0 BCDMEE+Arial-ItalicMT TrueType WinAnsi yes yes no 237 0 ArialMT TrueType WinAnsi no no no 241 0 SymbolMT TrueType WinAnsi no no no 244 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 262 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 266 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 270 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 274 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 281 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 288 0 BCDMEE+Arial-ItalicMT TrueType WinAnsi yes yes no 296 0 BCDNEE+ArialMT CID TrueType Identity-H yes yes yes 300 0 ArialMT TrueType WinAnsi no no no 308 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-12-19 02:51:46 CET RepresentationInformation: 302111.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-12-18 10:50:43 CET Size: 2066760 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 499 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: Design of the Study Destination: subsection.2.1 Item: Title: Generation of a Suitable anti-CSDE1 Monoclonal Antibody Destination: subsection.2.2 Item: Title: Global CSDE1 Levels Decrease with Melanoma Malignancy Destination: subsection.2.3 Item: Title: CSDE1 Cytoplasmic/Nuclear Ratio Correlates with Disease-Specific Survival Destination: subsection.2.4 Item: Title: Discussion Destination: section.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Ethical Statement Destination: subsection.4.1 Item: Title: Immunohistochemistry (IHC) of Human Tissue Specimens Destination: subsection.4.2 Item: Title: Immunocytochemistry (ICC) Destination: subsection.4.3 Item: Title: Visual and Digital Quantification Destination: subsection.4.4 Item: Title: Statistical Analysis Destination: subsection.4.5 Item: Title: Cell Culture and Depletion Destination: subsection.4.6 Item: Title: References Destination: appendix.A. Info: Title: CSDE1 Intracellular Distribution as a Biomarker of Melanoma Prognosis Author: Alberto Indacochea, Tanit Guitart, Aram Boada, Vicente Peg, Ariadna Quer, Hafid Laayouni, Laura Condal, Pablo Espinosa, Jose Luis Manzano and Fátima Gebauer Subject: RNA-binding proteins are emerging as critical modulators of oncogenic cell transformation, malignancy and therapy resistance. We have previously found that the RNA-binding protein Cold Shock Domain containing protein E1 (CSDE1) promotes invasion and metastasis of melanoma, the deadliest form of skin cancer and also a highly heterogeneous disease in need of predictive biomarkers and druggable targets. Here, we design a monoclonal antibody useful for IHC in the clinical setting and use it to evaluate the prognosis potential of CSDE1 in an exploratory cohort of 149 whole tissue sections including benign nevi and primary tumors and metastasis from melanoma patients. Contrary to expectations for an oncoprotein, we observed a global decrease in CSDE1 levels with increasing malignancy. However, the CSDE1 cytoplasmic/nuclear ratio exhibited a positive correlation with adverse clinical features of primary tumors and emerged as a robust indicator of progression free survival in cutaneous melanoma, highlighting the potential of CSDE1 as a biomarker of prognosis. Our findings provide a novel feature for prognosis assessment and highlight the intricacies of RNA-binding protein dynamics in cancer progression. 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