Division of Urology, Department of Surgery, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan.
Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
J Cell Mol Med. 2024 Aug;28(16):e70041. doi: 10.1111/jcmm.70041.
Age, ethnic background and genetic components have been identified as the established risks for prostate cancer (PCa). Pentraxin 3 (PTX3), originally identified as a pattern-recognition molecule for defence against infectious agents, has multiple functions in tissue repair and in the regulation of cancer-associated inflammation. In this study, we sought to investigate the impact of PTX3 gene variants on the development of PCa. Genotypes of four common single-nucleotide polymorphisms (SNPs) of PTX3 gene, including rs1840680, rs2305619, rs3816527 and rs2120243, were profiled among 705 PCa patients and 705 ethnicity-matched controls. In this study, we found that patients who carry at least one minor allele (C) of rs3816527 (AC and CC) tended to develop advanced forms of diseases (clinical large T stage, OR, 1.593, p = 0.032; pathologically-confirmed nodal spread, OR, 1.987, p = 0.011; metastatic tumour, OR, 3.896, p = 0.032) as compared with those homologous for the major allele (AA). Further stratification analysis showed that such association of rs3816527 with lymphatic and distal metastasis of PCa was accentuated in the younger age group (≤65 at diagnosis) but not seen in the older age group (>65 at diagnosis), suggesting an age-specific effect of PTX3 variants. Prediction of PTX3 protein structure implied that polymorphism may alter the quaternary organization and oligomerization of PTX3 protein. Moreover, our gene silencing experiments and survey of public datasets revealed that elevation of PTX3 levels in PCa was required for cell migration and associated with tumour metastasis. Our results highlight an association of PTX3 rs3816527 with the progression of PCa.
年龄、种族背景和遗传因素已被确定为前列腺癌 (PCa) 的既定风险因素。Pentraxin 3 (PTX3) 最初被鉴定为一种针对感染因子的防御模式识别分子，在组织修复和调节与癌症相关的炎症中具有多种功能。在这项研究中，我们试图研究 PTX3 基因变异对 PCa 发展的影响。在 705 名 PCa 患者和 705 名种族匹配的对照中，对 PTX3 基因的四个常见单核苷酸多态性 (SNP) 的基因型进行了分析，包括 rs1840680、rs2305619、rs3816527 和 rs2120243。在这项研究中，我们发现至少携带一个 minor allele (C) 的 rs3816527 (AC 和 CC) 患者倾向于发展为疾病的晚期形式 (临床大 T 期，OR，1.593，p=0.032；经病理证实的淋巴结转移，OR，1.987，p=0.011；转移性肿瘤，OR，3.896，p=0.032)，与主要等位基因 (AA) 相同的患者相比。进一步的分层分析表明，rs3816527 与 PCa 的淋巴和远处转移的关联在年轻年龄组（诊断时≤65 岁）中更为明显，但在老年年龄组（诊断时>65 岁）中未见，表明 PTX3 变异具有年龄特异性效应。PTX3 蛋白结构的预测表明，多态性可能改变 PTX3 蛋白的四级结构和寡聚化。此外，我们的基因沉默实验和公共数据集的调查表明，PCa 中 PTX3 水平的升高是细胞迁移所必需的，并与肿瘤转移相关。我们的结果强调了 rs3816527 与 PCa 进展的关联。
