Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
J Cell Mol Med. 2024 Apr;28(8):e18229. doi: 10.1111/jcmm.18229.
Monoamine oxidase B (MAOB), a neurotransmitter-degrading enzyme, was reported to reveal conflicting roles in various cancers. However, the functional role of MAOB and impacts of its genetic variants on prostate cancer (PCa) is unknown. Herein, we genotyped four loci of MAOB single-nucleotide polymorphisms (SNPs), including rs1799836 (A/G), rs3027452 (G/A), rs6651806 (A/C) and rs6324 (G/A) in 702 PCa Taiwanese patients. We discovered that PCa patients carrying the MAOB rs6324 A-allele exhibited an increased risk of having a high initial prostate-specific antigen (iPSA) level (>10 ng/mL). Additionally, patients with the rs3027452 A-allele had a higher risk of developing distal metastasis, particularly in the subpopulation with high iPSA levels. In a subpopulation without postoperative biochemical recurrence, patients carrying the rs1799836 G-allele had a higher risk of developing lymph node metastasis and recurrence compared to those carrying the A-allele. Furthermore, genotype screening in PCa cell lines revealed that cells carrying the rs1799836 G-allele expressed lower MAOB levels than those carrying the A-allele. Functionally, overexpression and knockdown of MAOB in PCa cells respectively suppressed and enhanced cell motility and proliferation. In clinical observations, correlations of lower MAOB expression levels with higher Gleason scores, advanced clinical T stages, tumour metastasis, and poorer prognosis in PCa patients were noted. Our findings suggest that MAOB may act as a suppressor of PCa progression, and the rs3027452 and rs1799836 genetic variants of MAOB are linked to PCa metastasis within the Taiwanese population.
单胺氧化酶 B（MAOB）是一种神经递质降解酶，据报道在各种癌症中具有矛盾的作用。然而，MAOB 的功能作用及其遗传变异对前列腺癌（PCa）的影响尚不清楚。在此，我们对 702 名台湾 PCa 患者的 MAOB 单核苷酸多态性（SNP）四个位点（rs1799836（A/G）、rs3027452（G/A）、rs6651806（A/C）和 rs6324（G/A））进行了基因分型。我们发现携带 MAOB rs6324 A 等位基因的 PCa 患者具有较高的初始前列腺特异性抗原（iPSA）水平（>10ng/mL）的风险。此外，携带 rs3027452 A 等位基因的患者发生远处转移的风险更高，特别是在 iPSA 水平较高的亚群中。在没有术后生化复发的亚群中，与携带 A 等位基因的患者相比，携带 rs1799836 G 等位基因的患者发生淋巴结转移和复发的风险更高。此外，在 PCa 细胞系中进行的基因型筛选显示，携带 rs1799836 G 等位基因的细胞表达的 MAOB 水平低于携带 A 等位基因的细胞。功能上，PCa 细胞中 MAOB 的过表达和敲低分别抑制和增强了细胞迁移和增殖。在临床观察中，发现 MAOB 表达水平较低与较高的 Gleason 评分、较高的临床 T 分期、肿瘤转移和 PCa 患者较差的预后相关。我们的研究结果表明，MAOB 可能作为 PCa 进展的抑制因子，MAOB 的 rs3027452 和 rs1799836 遗传变异与台湾人群中 PCa 的转移有关。
