CXCL12/CXCR4轴的等位基因变异和免疫染色特征:与前列腺癌预后相关性的调查研究。
Allelic variants and immunostaining profile in CXCL12/CXCR4 axis: An investigation of association with prognosis in prostate cancer.
发表日期:2023 Sep 12
作者:
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
来源:
Parasites & Vectors
摘要:
前列腺癌(PCa)是最常见的男性恶性肿瘤,也是一个重要的死亡原因。它可以通过前列腺特异性抗原(PSA)血清水平和直肠指检来检测,但症状通常在进展期和转移期出现。C-X-C基序趋化因子配体12/C-X-C基序趋化因子受体4(CXCL12/CXCR4)轴参与细胞迁移,可能与转移过程有关。在这个背景下,本研究的目的是评估rs1801157(CXCL12)和rs2228014(CXCR4)的等位基因变异以及CXCR4蛋白的免疫组织化学染色作为前列腺癌预后标志物的候选者。样本(n = 60)根据预后参数(诊断时是否有转移)分为三组:预后较好、预后较差且诊断时有转移、预后较差且诊断时没有转移,并通过间接免疫组织化学评估CXCR4免疫染色,考虑来自同一患者的肿瘤和邻近组织(n = 120)。发现rs2228014(CXCR4)的C等位基因与前列腺腺外生长呈显著关联。对于CXCR4的免疫组织化学染色,弱标记和胞浆定位为主,并且在恶性组织与邻近组织之间存在显著差异,恶性组织中的蛋白质表达更高。发现CXCR4瘤内免疫染色与TNM分期(T2b-T2c)和PSA水平(>20 ng/mL)呈显著相关。没有任何等位基因变异影响CXCR4的免疫染色。预后组在等位基因频率和免疫染色特征上没有差异。这些结果表明,CXCR4受体可能是恶性前列腺癌预后恶化的途径之一。版权所有 © 2023 Elsevier GmbH。保留所有权利。
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.Copyright © 2023 Elsevier GmbH. All rights reserved.