Association of doublecortin-like kinase 1 with tumor aggressiveness and poor biochemical recurrence-free survival in prostate cancer.
Association of doublecortin-like kinase 1 with tumor aggressiveness and poor biochemical recurrence-free survival in prostate cancer.
复制标题
双皮质素样激酶 1 与前列腺癌肿瘤侵袭性和不良生化无复发生存率的关系
DOI：
10.2147/ott.s157295
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发表时间：
2018
影响因子：
4
通讯作者：
Pang J
中科院分区：
文献类型：
--
作者：
Jiang D;Xiao C;Xian T;Wang L;Mao Y;Zhang J;Pang J
背景双重皮质醇样激酶1(DCLK1)已被证实与多种肿瘤有关，但其在前列腺癌(PCa)中的作用尚不清楚。本研究旨在探讨DCLK1在PCa中的表达规律及预后价值。方法采用实时定量聚合酶链式反应和免疫印迹方法检测25例PCa和良性前列腺增生症(BPH)新鲜标本及PCa细胞系中DCLK1mRNA和蛋白的表达水平。采用免疫组织化学(IHC)法检测125例PCa和65例BPH组织中DCLK1的表达。统计分析DCLK1表达与前列腺癌根治术后临床病理参数及生化复发(BCR)的关系。此外，通过四甲基偶氮唑盐比色法和Transwell法检测DCLK1在PCa细胞增殖、迁移和侵袭中的作用。结果DCLK1在PCa新鲜组织中的表达水平明显高于BPH组织。一致地，IHC显示与BPH相比，DCLK1在PCa石蜡包埋组织中的表达增加。DCLK1的表达与术后Gleason分级(P=0.012)、病理T分期(P=0.001)、精囊侵犯(P=0.026)和淋巴结转移(P=0.017)显著相关。Kaplan-Meier曲线分析显示，DCLK1的高表达与术后无BCR生存期(BRF)降低有关。多因素COX分析显示，术后Gleason分级(P=0.018)、病理T分期(P<；0.001)、精囊侵犯(P=0.012)、淋巴结转移(P=0.014)、DCLK1表达(P=0.014)是影响BCR的独立因素。在体外，DCLK1在PCa细胞系中的过表达和下调表明DCLK1可以促进细胞的增殖、迁移和侵袭。结论DCLK1的高表达与PCa的侵袭性有关，可独立预测PCa患者的不良BRF。
Background 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. Patients and methods 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. Results 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 (P=0.012), pathological T stage (P=0.001), seminal vesicle invasion (P=0.026), and lymph node involvement (P=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 (P=0.018), pathological T stage (P<0.001), seminal vesicle invasion (P=0.012), lymph node involvement (P=0.014), and DCLK1 expression (P=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. Conclusion Increased DCLK1 expression is associated with PCa aggressiveness and may independently predict poor bRFS in patients with PCa.