Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Department of Gynecology and Obstetrics, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
Mol Med Rep. 2018 Dec;18(6):5327-5336. doi: 10.3892/mmr.2018.9562. Epub 2018 Oct 16.
Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. LIN28 homolog A (LIN28A) is a RNA‑binding protein, which serves a fundamental role in cell development and pluripotency. Polo‑like kinase 4 (PLK4) is a member of the polo‑like kinase family, which primarily takes part in the mitotic regulation. Overexpression of LIN28A has been demonstrated in ovarian cancer; however, the expression of PLK4 and the correlation between the expression of LIN28A and PLK4 in EOC has not been discussed. In the present study, the mRNA and protein levels of LIN28A and PLK4 were evaluated by reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry in ovarian tissues of patients. Results demonstrated significantly increased expression in EOC compared with benign epithelial ovarian tumors. High expression of LIN28A and PLK4 was detected at the advanced pathological stage. Furthermore, PLK4 expression was positively correlated with LIN28A (r=0.555; P=0.039). The median survival analysis of patients with EOC with LIN28A and PLK4 double positive expression was 14 months, compared with 30 months in single positive and 60 months in double negative patients by Kaplan‑Meier analysis (P<0.05). The expressions of LIN28A and PLK4 was elevated in different EOC cell lines compared to with a normal ovarian cell line. The 293T cells transfected with LIN28A plus a PLK4 plasmid were the fastest‑growing group. These results suggest that co‑expression of LIN28A and PLK4 may be associated with poor prognosis of EOC and could serve as promising prognostic biomarkers and therapeutic targets in EOC. LIN28A and PLK4 may be used along with traditional morphological and clinical characteristics for predicting prognosis.
上皮性卵巢癌（EOC）是最致命的妇科恶性肿瘤。LIN28 同源物 A（LIN28A）是一种 RNA 结合蛋白，在细胞发育和多能性中发挥着基本作用。丝氨酸/苏氨酸蛋白激酶 4（PLK4）是丝氨酸/苏氨酸蛋白激酶家族的成员，主要参与有丝分裂调控。已经证实 LIN28A 在卵巢癌中过表达；然而，PLK4 的表达以及 EOC 中 LIN28A 和 PLK4 表达之间的相关性尚未得到讨论。在本研究中，通过逆转录-定量聚合酶链反应和免疫组织化学法评估了卵巢组织中 LIN28A 和 PLK4 的 mRNA 和蛋白水平。结果显示，与良性上皮性卵巢肿瘤相比，EOC 中表达显著增加。高级别病理分期检测到 LIN28A 和 PLK4 高表达。此外，PLK4 表达与 LIN28A 呈正相关（r=0.555；P=0.039）。Kaplan-Meier 分析显示，EOC 患者 LIN28A 和 PLK4 双阳性表达患者的中位生存时间为 14 个月，而单阳性患者为 30 个月，双阴性患者为 60 个月（P<0.05）。与正常卵巢细胞系相比，不同 EOC 细胞系中 LIN28A 和 PLK4 的表达均升高。转染 LIN28A 加 PLK4 质粒的 293T 细胞生长最快。这些结果表明，LIN28A 和 PLK4 的共表达可能与 EOC 的不良预后有关，并可能成为 EOC 有前途的预后生物标志物和治疗靶点。LIN28A 和 PLK4 可与传统的形态学和临床特征一起用于预测预后。
