bfb64b5424aaabbf67c4c65bd915be78 ijms-26-04669.pdf 246cf28da0522c5ad73dd6c506844f20421b4cea ijms-26-04669.pdf c9a660aa96722cf02a137506a1772ac587de3e20dcf5b343368bbc0307ba6b32 ijms-26-04669.pdf Title: Pilot Investigation on Markers of Bone Metabolism, Angiogenesis, and Neuroendocrine Activity as Potential Predictors of Survival of Metastatic Prostate Cancer Patients with Bone Metastases Subject: Prostate cancer with bone metastasis exhibits significant heterogeneity, complicating prognosis, and treatment. This study explores the potential of plasma, serum, and urine biomarkers to stratify patients and evaluate their prognostic value. Using two-step clustering, we analyzed baseline levels of Platelet-derived growth factor-BB (PDGF-BB), Insulin-like growth factor-binding protein 1 (IGFBP-1), Bone Morphogenetic Protein 2 (BMP-2), Vascular endothelial growth factor (VEGF) (plasma and urine), prostate-specific antigen (PSA), neuron-specific enolase (NSE), chromogranin A (CgA) and bone-specific alkaline phosphatase (BAP) (serum) and creatinine (Cr), and type I collagen-cross-linked N telopeptide (NTx) (urine) in 29 patients with prostate cancer and bone metastasis. Longitudinal biomarker dynamics were assessed at baseline, 6 months, and 12 months. Clinical outcomes were evaluated using Kaplan–Meier and multivariate analyses. Three distinct groups (C1, C2, and C3) were identified. C1 exhibited elevated pPDGF-BB and pVEGF levels, C3 had increased pBAP and uNTx/Cr, and C2 showed lower biomarker levels. Prior treatments influenced biomarker levels, with bisphosphonates reducing bone turnover markers and radiotherapy correlating with long-term changes in growth factors. Longitudinal analysis revealed unique biomarker dynamics within each group, with a tendency for pPDGF-BB and pVEGF levels to decrease over time in C1, and distinct trends in uNTx/Cr between groups. Despite individual biomarkers failing to predict survival, C3 patients demonstrated significantly worse survival than C1 and C2. Molecular clustering of peripheral blood and urinary biomarkers identifies distinct subgroups with metastatic castration-resistant prostate cancer patients outperforming traditional models in outcome prediction and supporting its potential for personalized treatment and prognosis. Keywords: biomarkers; prostate cancer; bone metastasis Author: Maria Angels Ortiz, Georgia Anguera, Elisabet Cantó, Jose Alejandre, Josefina Mora, Ruben Osuna-Gómez, Maria Mulet, Pradip Mora, Assumpta Antonijuan, Sofia Sánchez, Ona Ramírez, Vanessa Orantes, Pablo Maroto and Silvia Vidal Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue May 13 16:25:54 2025 CEST ModDate: Tue May 13 16:28:32 2025 CEST 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: 1846767 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- QUGTTK+URWPalladioL-Roma Type 1 Custom yes yes yes 10 0 MPSXCM+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 LAUSTY+URWPalladioL-Ital Type 1 Custom yes yes yes 21 0 OVNEXW+EURM10 Type 1 Builtin yes yes yes 50 0 UWJUYN+CMSY10 Type 1 Builtin yes yes yes 55 0 APCBAN+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 66 0 APCBCO+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 72 0 APCBCP+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 78 0 APCBDP+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 84 0 APCBEA+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 87 0 APCBEB+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 90 0 APCCDN+PalatinoLinotype-Roman TrueType MacRoman yes yes no 93 0 APCBAN+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 103 0 APCBCO+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 109 0 APCBCP+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 115 0 APCBDP+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 121 0 APCBEA+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 124 0 APCBEB+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 127 0 APCCDN+PalatinoLinotype-Roman TrueType MacRoman yes yes no 130 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes yes 271 0 MDIKPC+CMBSY10 Type 1 Builtin yes yes yes 279 0 EUQOAW+EURM7 Type 1 Builtin yes yes yes 284 0 APCBAN+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 295 0 APCBCO+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 301 0 APCBCP+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 307 0 APCBDP+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 313 0 APCBEA+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 316 0 APCBEB+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 319 0 APCCDN+PalatinoLinotype-Roman TrueType MacRoman yes yes no 322 0 APCBAN+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 333 0 APCBCO+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 339 0 APCBCP+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 345 0 APCBDP+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 351 0 APCBEA+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 354 0 APCBEB+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 357 0 APCCDN+PalatinoLinotype-Roman TrueType MacRoman yes yes no 360 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-10-22 03:09:34 CEST RepresentationInformation: ijms-26-04669.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-10-21 17:17:35 CEST Size: 1846767 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 611 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: Clinical and Demographic Characteristics of Patients Destination: subsection.2.1 Item: Title: Identification of Molecular Clusters and Key Biomarkers Destination: subsection.2.2 Item: Title: Influence of Clinical Factors and Prior Treatments on Biomarker Levels Destination: subsection.2.3 Item: Title: Biomarker Dynamics Destination: subsection.2.4 Item: Title: Prognostic Implications Destination: subsection.2.5 Item: Title: Discussion Destination: section.3 Item: Title: Material and Methods Destination: section.4 Children: Item: Title: Patients Destination: subsection.4.1 Item: Title: Determination of Plasma, Serum, and Urine Markers Destination: subsection.4.2 Item: Title: Statistical Analysis Destination: subsection.4.3 Item: Title: References Destination: appendix.A. Info: Title: Pilot Investigation on Markers of Bone Metabolism, Angiogenesis, and Neuroendocrine Activity as Potential Predictors of Survival of Metastatic Prostate Cancer Patients with Bone Metastases Author: Maria Angels Ortiz, Georgia Anguera, Elisabet Cantó, Jose Alejandre, Josefina Mora, Ruben Osuna-Gómez, Maria Mulet, Pradip Mora, Assumpta Antonijuan, Sofia Sánchez, Ona Ramírez, Vanessa Orantes, Pablo Maroto and Silvia Vidal Subject: Prostate cancer with bone metastasis exhibits significant heterogeneity, complicating prognosis, and treatment. This study explores the potential of plasma, serum, and urine biomarkers to stratify patients and evaluate their prognostic value. Using two-step clustering, we analyzed baseline levels of Platelet-derived growth factor-BB (PDGF-BB), Insulin-like growth factor-binding protein 1 (IGFBP-1), Bone Morphogenetic Protein 2 (BMP-2), Vascular endothelial growth factor (VEGF) (plasma and urine), prostate-specific antigen (PSA), neuron-specific enolase (NSE), chromogranin A (CgA) and bone-specific alkaline phosphatase (BAP) (serum) and creatinine (Cr), and type I collagen-cross-linked N telopeptide (NTx) (urine) in 29 patients with prostate cancer and bone metastasis. Longitudinal biomarker dynamics were assessed at baseline, 6 months, and 12 months. Clinical outcomes were evaluated using Kaplan Meier and multivariate analyses. Three distinct groups (C1, C2, and C3) were identified. C1 exhibited elevated pPDGF-BB and pVEGF levels, C3 had increased pBAP and uNTx/Cr, and C2 showed lower biomarker levels. Prior treatments influenced biomarker levels, with bisphosphonates reducing bone turnover markers and radiotherapy correlating with long-term changes in growth factors. Longitudinal analysis revealed unique biomarker dynamics within each group, with a tendency for pPDGF-BB and pVEGF levels to decrease over time in C1, and distinct trends in uNTx/Cr between groups. Despite individual biomarkers failing to predict survival, C3 patients demonstrated significantly worse survival than C1 and C2. Molecular clustering of peripheral blood and urinary biomarkers identifies distinct subgroups with metastatic castration-resistant prostate cancer patients outperforming traditional models in outcome prediction and supporting its potential for personalized treatment and prognosis. 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