Fellowship Gynecology Oncology Division, Department of Obstetrics and Gynecology, Universitas Indonesia, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine, Jakarta, Indonesia.
Department of Obstetrics and Gynecology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito Hospital, Yogyakarta, Indonesia.
Asian Pac J Cancer Prev. 2021 Dec 1;22(12):4057-4065. doi: 10.31557/APJCP.2021.22.12.4057.
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.
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.
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.
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.
在宫颈癌中，预后生物标志物得到了广泛研究，包括癌症干细胞（CSC）标志物。然而，其意义仍不确定。本研究旨在确定宫颈癌干细胞（CCSC）标志物对生存的作用。
我们按照 PRISMA 指南，对报道 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（PROSPERO CRD42021237072）。我们纳入了来自 PubMed、EBSCO 和 The Cochrane Library 数据库的研究，这些研究调查了组织肿瘤中 CCSCs 表达与总生存（OS）或无病生存（DFS）之间的关系。根据纽卡斯尔-渥太华质量评估量表分析研究的质量。
从 413 篇出版物中，经过包括和排除标准的研究选择后，纳入了 22 项研究。CSC 标志物的高表达与较差的 OS 和 DFS 相关（HR=1.05，95%CI：1.03-1.07，P<0.0001；HR=1.31，95%CI：1.09-1.17，P<0.00001）。对个别 CCSC 标志物的亚组分析表明，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<0.0008）、ALDH1（HR=1.36，95%CI：1.13-1.64，P<0.001）和 CD49f（HR=3.02，95%CI：1.37-6.64，P<0.006）与较差的 OS 相关；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）和 ALDH1（HR=1.22，95%CI：1.10-1.35，P<0.0002）与较差的 DFS 相关。由于仅有一项研究调查了 MSI-1 和 CK17 标志物，因此我们未对其进行荟萃分析。
OCT4、SOX2 和 ALDH1 的表达与宫颈癌组织中的 OS 和 DFS 不良相关。这些标志物可能具有作为预后生物标志物的潜力，以预测不良生存。
