Kim Mee Young, Jung Ae Ryang, Kim Ga Eun, Yang Jonghyup, Ha U-Syn, Hong Sung-Hoo, Choi Yeong Jin, Moon Mi Hyoung, Kim Sae Woong, Lee Ji Youl, Park Yong Hyun
Department of Urology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea.
Cancer Research Institute, College of Medicine, The Catholic University of Korea.
J Cancer. 2019 Jan 1;10(3):749-756. doi: 10.7150/jca.28099. eCollection 2019.
We aimed to investigate the expression of FOXM1 and to determine the relationships between FOXM1 expression and clinicopathologic characteristics in patients with PCa. Furthermore, we reconfirmed the prognostic impact of FOXM1 in different cohorts using already published data. Formalin-fixed, paraffin-embedded tissues were collected from patients with low- (n=17), intermediate- (n=36), and high-risk (n=29) disease, from patients with CRPC (n=2) and from patients with BPH (n=28). To analyze FOXM1 expression, we performed IHC analyses. Also, we analyzed gene expression data from cBioPortal to evaluate the associations between FOXM1 alteration and prognosis of PCa. FOXM1 expression measured using Allred score differed between patients with BPH, and low-, intermediate-, and high-risk PCa (0.3, 1.5, 4.8, and 6.2, respectively; p<0.001). Patients with high FOXM1 expression had higher preoperative PSA levels (p=0.023), more advanced tumor stages (p=0.047), and higher pathologic Gleason score (p<0.001) than those with low FOXM1 expression. ROC curve analysis indicated that FOXM1 expression was a useful marker for discriminating PCa from BPH (AUC 0.851, 95% CI 0.783-0.920) and for discriminating high-risk PCa from low- and intermediate-risk PCa (AUC 0.807, 95% CI 0.719-0.894). In multivariate analyses, high FOXM1 expression was an independent predictor of BCR. Finally, in the TCGA dataset, FOXM1 alteration was associated with poor overall (p=4.521e) and disease-free survival (p=0.0108). In patients with PCa, high FOXM1 expression was associated with advanced tumor stages, high Gleason score, and poor prognosis. These data suggest a role of FOXM1 in biologically and clinically aggressive PCa.
我们旨在研究FOXM1的表达情况，并确定前列腺癌（PCa）患者中FOXM1表达与临床病理特征之间的关系。此外，我们利用已发表的数据在不同队列中再次证实了FOXM1的预后影响。从低危（n = 17）、中危（n = 36）和高危（n = 29）疾病患者、去势抵抗性前列腺癌（CRPC）患者（n = 2）以及良性前列腺增生（BPH）患者（n = 28）中收集福尔马林固定、石蜡包埋组织。为分析FOXM1表达，我们进行了免疫组化（IHC）分析。此外，我们分析了来自cBioPortal的基因表达数据，以评估FOXM1改变与PCa预后之间的关联。使用奥尔雷德评分法测量的FOXM1表达在BPH患者以及低危、中危和高危PCa患者之间存在差异（分别为0.3、1.5、4.8和6.2；p<0.001）。与低FOXM1表达患者相比，高FOXM1表达患者术前前列腺特异性抗原（PSA）水平更高（p = 0.023），肿瘤分期更晚（p = 0.047），病理Gleason评分更高（p<0.001）。ROC曲线分析表明，FOXM1表达是区分PCa与BPH的有用标志物（曲线下面积[AUC] 0.851，95%置信区间[CI] 0.783 - 0.920），也是区分高危PCa与低危和中危PCa的有用标志物（AUC 0.807，95% CI 0.719 - 0.894）。在多因素分析中，高FOXM1表达是生化复发（BCR）的独立预测因子。最后，在癌症基因组图谱（TCGA）数据集中，FOXM1改变与总生存期较差（p = 4.521e）和无病生存期较差（p = 0.0108）相关。在PCa患者中，高FOXM1表达与肿瘤分期晚、Gleason评分高及预后差相关。这些数据表明FOXM1在生物学和临床上侵袭性PCa中发挥作用。
