叉头框蛋白 O1（FOXO1）和配对盒基因 3（PAX3）过表达与宫颈癌患者的不良预后相关。
Forkhead box protein O1 (FOXO1) and paired box gene 3 (PAX3) overexpression is associated with poor prognosis in patients with cervical cancer.
机构信息
Department of Obstetrics and Gynecology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seoul, 03722, South Korea.
Department of Obstetrics and Gynecology, Gangnam Severance Hospital, 20 Eonjuro 63-gil, Seoul, 06229, South Korea.
出版信息
Int J Clin Oncol. 2019 Nov;24(11):1429-1439. doi: 10.1007/s10147-019-01507-w. Epub 2019 Jul 13.
PURPOSE
Forkhead box protein O1 (FOXO1) and paired box gene 3 (PAX3) have been reported to play an imported role in human cancers, but their role in cervical cancer has not yet been clarified. In this study, we evaluated the functional role of FOXO1 in cervical cancer cells and investigated the expression and clinical significance of FOXO1 and PAX3 in cervical lesions.
METHODS
In vitro assessment of cell function by cell viability, migration, and invasion assays were performed on FOXO1-knockdown cervical cancer cells. Immunohistochemical (IHC) staining analyses of FOXO1 and PAX3 were performed with a tissue microarray (TMA). The clinical significance was evaluated by comparing the data with various clinicopathologic characteristics, including survival of patients with cervical cancer.
RESULTS
In vitro results revealed that knockdown of FOXO1 is associated with decreased cell viability (p < 0.001), migration (p < 0.001), and invasion (p < 0.05), supporting the oncogenic role of FOXO1 in cervical cancer. FOXO1 and PAX3 expression was significantly higher in CIN (both p < 0.001) and cancer tissue (both p < 0.001) than in normal tissue. Multivariate analysis indicated that FOXO1 expression (hazard ratio 4.01 [95% CI 1.22-13.10], p = 0.021) and an advanced FIGO stage (hazard ratio 3.89 [95% CI 1.35-11.19], p = 0.012) were independent prognostic factors for overall survival.
CONCLUSIONS
This study reveals increased FOXO1 and PAX3 expression in cervical cancers and indicates an oncogenic role of FOXO1 in cervical cancer cells that correlates with poor patient survival.
目的
叉头框蛋白 O1（FOXO1）和配对盒基因 3（PAX3）已被报道在人类癌症中发挥重要作用，但它们在宫颈癌中的作用尚未阐明。本研究评估了 FOXO1 在宫颈癌细胞中的功能作用，并研究了 FOXO1 和 PAX3 在宫颈病变中的表达及其临床意义。
方法
采用细胞活力、迁移和侵袭实验，在 FOXO1 敲低的宫颈癌细胞中进行体外评估细胞功能。采用组织微阵列（TMA）进行 FOXO1 和 PAX3 的免疫组织化学（IHC）染色分析。通过与宫颈癌患者的各种临床病理特征（包括生存数据）进行比较，评估临床意义。
结果
体外结果表明，FOXO1 敲低与细胞活力降低（p<0.001）、迁移（p<0.001）和侵袭（p<0.05）相关，支持 FOXO1 在宫颈癌中的致癌作用。FOXO1 和 PAX3 的表达在 CIN（均 p<0.001）和癌症组织（均 p<0.001）中均显著高于正常组织。多因素分析表明，FOXO1 表达（危险比 4.01 [95%CI 1.22-13.10]，p=0.021）和 FIGO 晚期分期（危险比 3.89 [95%CI 1.35-11.19]，p=0.012）是总生存的独立预后因素。
结论
本研究揭示了宫颈癌中 FOXO1 和 PAX3 表达增加，并表明 FOXO1 在宫颈癌细胞中具有致癌作用，与患者生存不良相关。
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