Jiang Donggen, Xiao Chutian, Xian Tuzeng, Wang Liantao, Mao Yunhua, Zhang Junfu, Pang Jun
Department of Urology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Department of General Surgery, Shenzhen Shajing Affiliated Hospital of Guangzhou Medical University, Shenzhen, China.
Onco Targets Ther. 2018 Feb 28;11:1077-1086. doi: 10.2147/OTT.S157295. eCollection 2018.
Doublecortin-like kinase 1 (DCLK1) has been proven to be involved in numerous tumors, while its role in prostate cancer (PCa) is still unclear. This study aimed at investigating the expression pattern and prognostic value of DCLK1 in PCa.
Real-time polymerase chain reaction and Western blot were employed to determine DCLK1 mRNA and protein levels in 25 paired fresh samples of PCa and benign prostatic hyperplasia (BPH) as well as in PCa cell lines. Immunohistochemistry (IHC) was also performed in 125 PCa and 65 BPH tissues to assess DCLK1 expression. Then, the association of DCLK1 expression with clinicopathological parameters and biochemical recurrence (BCR) after radical prostatectomy was statistically analyzed. In addition, the role of DCLK1 in PCa cell proliferation, migration, and invasion was evaluated by using MTT and transwell assays.
The mRNA and protein levels of DCLK1 were markedly higher in the fresh samples of PCa than that in BPH. Consistently, IHC revealed increased expression of DCLK1 in PCa paraffin-embedded tissues compared with BPH. Moreover, increased DCLK1 expression was significantly associated with postoperative Gleason grading (=0.012), pathological T stage (=0.001), seminal vesicle invasion (=0.026), and lymph node involvement (=0.017), respectively. The Kaplan-Meier curve analysis demonstrated that high DCLK1 expression was associated with lower postoperative BCR-free survival (bRFS). Furthermore, multivariate Cox analysis showed that postoperative Gleason grading (=0.018), pathological T stage (<0.001), seminal vesicle invasion (=0.012), lymph node involvement (=0.014), and DCLK1 expression (=0.014) were independent predictors of BCR. In vitro, the overexpression and knockdown of DCLK1 in PCa cell lines indicated that DCLK1 could promote cell proliferation, migration, and invasion.
Increased DCLK1 expression is associated with PCa aggressiveness and may independently predict poor bRFS in patients with PCa.
双皮质素样激酶1（DCLK1）已被证明与多种肿瘤有关，但其在前列腺癌（PCa）中的作用仍不清楚。本研究旨在探讨DCLK1在PCa中的表达模式及预后价值。
采用实时聚合酶链反应和蛋白质免疫印迹法检测25对PCa新鲜样本和良性前列腺增生（BPH）样本以及PCa细胞系中DCLK1的mRNA和蛋白水平。还对125例PCa组织和65例BPH组织进行免疫组织化学（IHC）检测以评估DCLK1的表达。然后，对DCLK1表达与前列腺癌根治术后临床病理参数及生化复发（BCR）的相关性进行统计学分析。此外，通过MTT和transwell实验评估DCLK1在PCa细胞增殖、迁移和侵袭中的作用。
PCa新鲜样本中DCLK1的mRNA和蛋白水平明显高于BPH。同样，免疫组化显示与BPH相比，PCa石蜡包埋组织中DCLK1表达增加。此外，DCLK1表达增加分别与术后Gleason分级（=0.012）、病理T分期（=0.001）、精囊侵犯（=0.026）和淋巴结受累（=0.017）显著相关。Kaplan-Meier曲线分析表明，DCLK1高表达与较低的术后无生化复发生存期（bRFS）相关。此外，多因素Cox分析显示，术后Gleason分级（=0.018）、病理T分期（<0.001）、精囊侵犯（=0.012）、淋巴结受累（=0.014）和DCLK1表达（=0.014）是BCR的独立预测因素。在体外，PCa细胞系中DCLK1的过表达和敲低表明DCLK1可促进细胞增殖、迁移和侵袭。
DCLK1表达增加与PCa侵袭性相关，可能独立预测PCa患者不良的bRFS。
