Wang Haoyuan, Li Sijie, Liu Bin, Wei Shufei, Wang Tianyi, Li Tao, Lin Jiahu, Ni Xiaochen
Department of Urology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
Oncol Lett. 2022 Jul 15;24(3):312. doi: 10.3892/ol.2022.13432. eCollection 2022 Sep.
Most prostate cancer (PCa) cases remain indolent with a relatively good prognosis. However, bone metastasis of PCa can quickly worsen prognoses and lead to mortality. Metastasis-free survival (MFS), a strong surrogate for overall survival, is widely used in PCa prognosis research. The present study identified molecules that affect bone MFS in PCa, with clinical validation. Three datasets (GSE32269, GSE74367 and GSE77930) were downloaded from the Gene Expression Omnibus database. Hub genes most relevant to clinical traits (bone metastasis-associated morbidity) were identified by weighted gene co-expression network analysis (WGCNA) and subjected to logistic regression analysis. Patient samples were obtained between January 2014 and December 2016, with a clinically annotated follow-up in December 2021. Clinical data and follow-up information for 60 patients with PCa were used in MFS analysis. Tumor samples were retrieved, and immunohistochemistry was performed to detect vascular endothelial growth factor (VEGF). The prognostic potential of the two molecules was assessed using Cox proportional hazards regression analysis. A total of 16 gene modules were obtained via WGCNA, and the tan module, containing 147 genes, was most closely linked to bone metastasis. In total, 877 differentially expressed genes (DEGs) were detected. The DEG-tan module intersection yielded seven hub genes [BUB1, kinesin family member (KIF)2C, RACGAP1, CENPE, KIF11, TTK and KIF20A]. Using univariate and multivariate logistic regression analyses for independent risk factors of bone metastasis, KIF11 and VEGF were found to be significantly associated with a higher T stage, prostate-specific antigen level and Gleason score. In addition, KIF11 and VEGF expression levels were positively correlated (P<0.001). Using univariate Cox analysis, KIF11 and VEGF were found to exhibit a significant association with poor MFS (P<0.05). However, only KIF11 was significantly associated with MFS upon multivariate analysis (P=0.007; hazard ratio, 2.776; 95% confidence interval, 1.315-5.859). Markers of bone metastasis in PCa were identified. Overall, KIF11 is an independent indicator that can predict bone metastasis for patients with PCa, which could be used to guide clinical practice.
大多数前列腺癌（PCa）病例进展缓慢，预后相对较好。然而，PCa的骨转移会迅速恶化预后并导致死亡。无转移生存期（MFS）是总生存期的有力替代指标，在PCa预后研究中被广泛应用。本研究通过临床验证，确定了影响PCa骨MFS的分子。从基因表达综合数据库下载了三个数据集（GSE32269、GSE74367和GSE77930）。通过加权基因共表达网络分析（WGCNA）确定了与临床特征（骨转移相关发病率）最相关的枢纽基因，并进行逻辑回归分析。在2014年1月至2016年12月期间获取患者样本，并于2021年12月进行临床注释随访。60例PCa患者的临床数据和随访信息用于MFS分析。收集肿瘤样本，进行免疫组织化学检测血管内皮生长因子（VEGF）。使用Cox比例风险回归分析评估这两种分子的预后潜力。通过WGCNA共获得16个基因模块，其中包含147个基因的棕褐色模块与骨转移关系最为密切。总共检测到877个差异表达基因（DEG）。DEG与棕褐色模块的交集产生了7个枢纽基因[BUB1、驱动蛋白家族成员（KIF）2C、RACGAP1、CENPE、KIF11、TTK和KIF20A]。通过对骨转移独立危险因素进行单因素和多因素逻辑回归分析，发现KIF11和VEGF与更高的T分期、前列腺特异性抗原水平和Gleason评分显著相关。此外，KIF11和VEGF表达水平呈正相关（P<0.001）。通过单因素Cox分析，发现KIF11和VEGF与不良MFS显著相关（P<0.05）。然而，多因素分析时只有KIF11与MFS显著相关（P=0.007；风险比，2.776；95%置信区间，1.315-5.859）。确定了PCa骨转移的标志物。总体而言，KIF11是一种独立指标，可预测PCa患者的骨转移，可用于指导临床实践。
