Yao Shasha, Shang Wenwen, Huang Lei, Xu Rui, Wu Ming, Wang Fang
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
National Key Clinical Department of Laboratory Medicine, 210029, Nanjing, China.
J Cancer. 2021 Jan 1;12(3):630-643. doi: 10.7150/jca.47278. eCollection 2021.
Ovarian cancer (OC) is the most lethal of gynecological tumors in women. Tumor metabolism has become a new opportunity in the treatment of tumors. Pyruvate dehydrogenase kinase 1 (PDK1), as a key regulatory enzyme implicated in metabolic reprogramming of tumors, abnormally high expressed in various tumors and involved in the regulation of tumor cell biological behavior. However, the role of PDK1 in the occurrence and development of ovarian cancer remains unclear. Our team identified the expression of PDK1 in ovarian cancer cell lines and tissues through RT-PCR and immunohistochemical staining and evaluated the correlation of PDK1 expression with clinicopathologic features of patients and survival analyses. We used a variety of experiments to explore the influence of PDK1 on proliferation, invasion, migration, colony formation, apoptosis and the cell cycle of ovarian cancer cell lines CAOV3 and SKOV3. PDK1 was highly expressed in ovarian cancer cell lines and OC tissues. High expression of PDK1 was closely correlated to tumor size, FIGO stage, extraovarian metastases status and distribution. Univariate and multivariate Cox regression analysis identified that PDK1 was an independent prognostic factor for overall survival. Moreover, PDK1 was a superior predictor in prognosis of ovarian cancer and the incorporation of CA125 into PDK1 generated a predictive combination that displayed better predictive accuracy for overall survival. Downregulation of PDK1 suppressed the biological behavior of ovarian cancer cells due to S phase arrest and cellular apoptosis. PDK1 may serve as a novel prognostic biomarker, even a promising antineoplastic target of ovarian cancer.
卵巢癌（OC）是女性妇科肿瘤中致死率最高的。肿瘤代谢已成为肿瘤治疗的新契机。丙酮酸脱氢酶激酶1（PDK1）作为参与肿瘤代谢重编程的关键调节酶，在多种肿瘤中异常高表达，并参与调节肿瘤细胞的生物学行为。然而，PDK1在卵巢癌发生发展中的作用仍不清楚。我们团队通过逆转录聚合酶链反应（RT-PCR）和免疫组织化学染色鉴定了PDK1在卵巢癌细胞系和组织中的表达，并评估了PDK1表达与患者临床病理特征及生存分析的相关性。我们采用多种实验来探究PDK1对卵巢癌细胞系CAOV3和SKOV3的增殖、侵袭、迁移、集落形成、凋亡及细胞周期的影响。PDK1在卵巢癌细胞系和OC组织中高表达。PDK1的高表达与肿瘤大小、国际妇产科联盟（FIGO）分期、卵巢外转移状态及分布密切相关。单因素和多因素Cox回归分析确定PDK1是总生存的独立预后因素。此外，PDK1在卵巢癌预后方面是一个更好的预测指标，将糖类抗原125（CA125）纳入PDK1可产生一个预测组合，该组合对总生存显示出更好的预测准确性。PDK1的下调由于S期阻滞和细胞凋亡而抑制了卵巢癌细胞的生物学行为。PDK1可能作为一种新型的预后生物标志物，甚至是卵巢癌有前景的抗肿瘤靶点。
