J Cancer 2021; 12(3):630-643. doi:10.7150/jca.47278

Research Paper

The oncogenic and prognostic role of PDK1 in the progression and metastasis of ovarian cancer

Shasha Yao1,2,3#, Wenwen Shang1,2#, Lei Huang1,2#, Rui Xu1,2, Ming Wu1,2, Fang Wang1,2✉

1. Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
2. National Key Clinical Department of Laboratory Medicine, 210029, Nanjing, China.
3. Department of Laboratory Medicine, the Affiliated Jiangning Hospital of Nanjing Medical University, 211100, Nanjing, China.
#These authors contributed equally to this article.

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Citation:
Yao S, Shang W, Huang L, Xu R, Wu M, Wang F. The oncogenic and prognostic role of PDK1 in the progression and metastasis of ovarian cancer. J Cancer 2021; 12(3):630-643. doi:10.7150/jca.47278. Available from https://www.jcancer.org/v12p0630.htm

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Abstract

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 in vitro 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.

Keywords: Pyruvate dehydrogenase kinase 1, ovarian cancer, tumor metabolic, biological behavior, prognostic biomarker