Allelic variants and immunostaining profile in CXCL12/CXCR4 axis: An investigation of association with prognosis in prostate cancer.

Abstract

Prostate cancer (PCa) is the malignant neoplasm that most commonly affects men and is an important cause of death. It can be detected by changes in serum levels of Prostate Specific Antigen (PSA) and digital rectal examination, but often symptoms do not appear until advanced stages and metastases. The C-X-C Motif Chemokine Ligand 12/C-X-C Motif Chemokine Receptor 4 (CXCL12/CXCR4) axis acts in cell migration and may be involved in the metastatic process. In this context, the aim of this study was to evaluate the allelic variants rs1801157 (CXCL12) and rs2228014 (CXCR4) and the immunostaining of CXCR4 protein as candidates for prognostic markers in PCa. Samples (n = 60) were divided according to prognostic parameters (with and without metastasis at diagnosis) in tree groups: better prognosis, worse prognosis with metastasis at diagnosis and worse prognosis without metastasis at diagnosis, and immunostaining was evaluated by indirect immunohistochemistry, considering tumoral and adjacent tissues from the same patient (n = 120). A significant association was found between the C allele of rs2228014 (CXCR4) and the extraprostatic extension. For CXCR4 immunostaining a weak labeling and a cytoplasmic localization predominated, as well as a significant difference between malignant versus adjacent tissue, with higher protein expression in the malignant tissue. A significant association was found between CXCR4 tumor immunostaining with TNM staging (T2b-T2c) and PSA level (> 20 ng/mL). None of the allelic variants affected CXCR4 immunostaining. Prognostic groups did not differ in allelic variant frequency or immunostaining profile. Findings suggest that CXCR4 receptor may be one of the ways to worsen the prognosis of prostatic cancer.

• Authors: Amanda Letícia Francelino, Érica Romão Pereira, Laís Capelasso Lucas Pinheiro, Adrielli Caroline Soares, Ana Carla Mendonça, Paulo Emílio Fuganti, Wilson Frantine-Silva, Karen Brajão de Oliveira, Juliana Mara Serpeloni, Roberta Losi Guembarovski
• Journal: Pathology, research and practice (Pathol Res Pract) Vol. 250 Pg. 154806 (Oct 2023) ISSN: 1618-0631 [Electronic] Germany
• PMID: 37738928 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier GmbH. All rights reserved.