目的:宫颈癌的预后生物标志物被广泛研究,包括癌症干细胞(CSC)标记。然而,其意义仍不确定。这项研究旨在确定宫颈癌干细胞(CCSC)标志物对生存的作用。
方法:我们根据PRISMA指南对报告CCSC标志物作为预后预测因子的研究进行了系统评价和荟萃分析(PROSPEROCRD42021237072)。我们纳入了研究组织肿瘤中CCSCs表达与PubMed的总生存期(OS)或无病生存期(DFS)的相关性的英文文章,EBSCO,和Cochrane图书馆数据库。采用纽卡斯尔-渥太华质量评价量表对研究质量进行分析。
结果:来自413种出版物,在根据纳入和排除标准进行研究选择后,包括22项研究。CMSC标志物的高表达与不良OS和DFS相关(分别为HR=1.05,95%CI:1.03-1.07,P<0.0001;HR=1.31,95%CI:1.09-1.17,P<0.00001)。单个CCSC标志物的亚分析显示CD44之间存在显著相关性(HR=1.14,95%CI:1.07-1.22,P0.0001),SOX2(HR=1.58,95%CI:1.17-2.14,P0.003),OCT4(HR=1.03,95%CI:1.01-1.06,P0.008),ALDH1(HR=1.36,95%CI:1.13-1.64,P0.001),和CD49f(HR=3.02,95%CI:1.37-6.64,P0.006),OS较差;OCT4(HR=1.14,95%CI1.06-1.22,P0.0003),SOX2(HR=1.11,95%CI:1.06-1.16,P<0.0001),和ALDH1(HR=1.22,95%CI:1.10-1.35,P0.0002),DFS较差。我们没有对MSI-1和CK17进行荟萃分析,因为只有一项研究调查了这些标志物。
结论:宫颈癌组织中OCT4、SOX2和ALDH1的表达与不良OS和DFS相关。这些标记物可能具有作为预测不良生存的预后生物标志物的潜在作用。
OBJECTIVE: Prognostic biomarkers in cervical cancer are widely investigated, including cancer stem cell (CSC) markers. However, their significance remains uncertain. This study aimed to determine the role of cervical cancer stem cell (CCSC) markers for survival.
METHODS: We conducted a systematic review and meta-analysis (PROSPERO CRD42021237072) of studies reporting CCSC markers as the prognostic predictor based on PRISMA guidelines. We included English articles investigating associations of CCSCs expression in tissue tumor with overall survival (OS) or disease-free survival (DFS) from PubMed, EBSCO, and The Cochrane Library databases. The quality of studies was analyzed based on Newcastle-Ottawa Quality Assessment Scale.
RESULTS: From 413 publications, after study selection with inclusion and exclusion criteria, 22 studies were included. High expressions of CCSC markers were associated with poor OS and DFS (HR= 1.05, 95% CI: 1.03 - 1.07, P <0.0001; HR= 1.31, 95% CI: 1.09 - 1.17, P <0.00001; respectively). Sub-analysis of individual CCSC markers indicated significant correlations between CD44 (HR= 1.14, 95% CI: 1.07 - 1.22, P 0.0001), SOX2 (HR= 1.58, 95% CI: 1.17 - 2.14, P 0.003), OCT4 (HR= 1.03, 95% CI: 1.01 - 1.06, P 0.008), ALDH1 (HR= 1.36, 95% CI: 1.13 - 1.64, P 0.001), and CD49f (HR= 3.02, 95% CI: 1.37 - 6.64, P 0.006) with worse OS; OCT4 (HR= 1.14, 95% CI 1.06 - 1.22, P 0.0003), SOX2 (HR= 1.11, 95% CI: 1.06 - 1.16, P <0.0001), and ALDH1 (HR= 1.22, 95% CI: 1.10 - 1.35, P 0.0002) with poor DFS. We did not conduct a meta-analysis for MSI-1 and CK17 because only one study investigated those markers.
CONCLUSIONS: Expressions of OCT4, SOX2, and ALDH1 were associated with poor OS and DFS in cervical cancer tissue. These markers might have potential roles as prognostic biomarkers to predict unfavorable survival.