Department of Urology and Urosurgery, University Medical Centre Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
Int J Mol Sci. 2020 Jun 19;21(12):4373. doi: 10.3390/ijms21124373.
Current outcome prediction markers for localized prostate cancer (PCa) are insufficient. The impact of the lipid-modifying Sphingomyelin Phosphodiesterase Acid Like 3B (SMPDL3B) in PCa is unknown. Two cohorts of patients with PCa who underwent radical prostatectomy ( = 40, = 56) and benign prostate hyperplasia (BPH) controls ( = 8, = 11) were profiled for expression with qRT-PCR. Publicly available PCa cohorts (Memorial Sloane Kettering Cancer Centre (MSKCC; = 131, = 29 controls) and The Cancer Genome Atlas (TCGA; = 497, = 53 controls)) served for validation. SMPDL3B's impact on proliferation and migration was analyzed in PC3 cells by siRNA knockdown. In both cohorts, a Gleason score and T stage independent significant overexpression of was seen in PCa compared to BPH ( < 0.001 each). A lower expression of was associated with a shorter overall survival (OS) ( = 0.005) in long term follow-up. A overexpression in PCa tissue was confirmed in the validation cohorts ( < 0.001 each). In the TCGA patients with low SMPDL3B expression, biochemical recurrence-free survival ( = 0.011) and progression-free interval ( < 0.001) were shorter. Knockdown of impaired PC3 cell migration but not proliferation ( = 0.0081). In summary, is highly overexpressed in PCa tissue, is inversely associated with localized PCa prognosis, and impairs PCa cell migration.
目前，局限性前列腺癌（PCa）的预后预测标志物还不够。脂质调节鞘磷脂磷酸二酯酶酸样 3B（SMPDL3B）在 PCa 中的作用尚不清楚。我们对接受根治性前列腺切除术的 PCa 患者和良性前列腺增生（BPH）对照者（n=40 和 n=56）以及 BPH 对照者（n=8 和 n=11）进行了 qRT-PCR 分析，以检测 SMPDL3B 的表达。我们使用了公共的 PCa 队列（纪念斯隆凯特琳癌症中心（MSKCC；n=131 和 n=29 对照组）和癌症基因组图谱（TCGA；n=497 和 n=53 对照组）来进行验证。通过 siRNA 敲低分析了 SMPDL3B 对 PC3 细胞增殖和迁移的影响。在两个队列中，与 BPH 相比，PCa 中均存在独立于 Gleason 评分和 T 分期的 SMPDL3B 过表达（均<0.001）。在长期随访中，SMPDL3B 表达水平较低与总生存期（OS）较短相关（n=0.005）。在验证队列中也证实了 PCa 组织中 SMPDL3B 的过表达（均<0.001）。在 TCGA 患者中，SMPDL3B 低表达者的生化无复发生存（n=0.011）和无进展间隔（<0.001）更短。SMPDL3B 敲低可损害 PC3 细胞的迁移，但不影响增殖（n=0.0081）。总之，SMPDL3B 在 PCa 组织中高表达，与局限性 PCa 预后呈负相关，并损害 PCa 细胞的迁移能力。
