Our previous study has suggested that the cell cycle-related kinase (CCRK) is a putative candidate oncogene in glioblastoma tumorigenesis. The potential oncogenic role of CCRK and its clinical/ prognostic significance, however, in ovarian carcinoma are unclear. In this study, CCRK expression was examined by immunohistochemistry in a series of ovarian carcinoma tissues. Overexpression of CCRK was detected in 53% of the ovarian carcinomas, and it was positively correlated with an ascending histological grade and/or advanced clinical stage of the disease (p < 0.05). In addition, overexpression of CCRK in ovarian carcinoma was determined to be a strong and an independent predictor of short overall survival (p < 0.05). In ovarian carcinoma cells, CCRK knockdown by RNAi led to a G1 phase cell cycle arrest, while CCRK overexpression by stable transfection of CCRK-containing plasmid pcDNA-CCRK promoted cell proliferation in vitro and tumor growth in vivo. In addition, CCRK knockdown was found to reduce cyclin D1 expression. Consistently, CCRK overexpression increased cyclin D1 expression, and furthermore, a significant correlation between expression of CCRK and cyclin D1 in ovarian carcinomas was observed (p < 0.001). These findings suggest a potential important role of CCRK in the control of cell proliferation via regulation of cyclin D1 expression, and the overexpression of CCRK, as detected by immunohistochemistry, is an independent molecular marker for shortened survival time of patients with ovarian carcinoma. ' UICCKey words: ovarian cancer; cell cycle-related kinase; prognosis; cell cycle; cyclin D1Ovarian cancer is 1 of the 5 leading causes of cancer-related deaths in women in the United States and Europe, 1 and is the leading cause of gynecologic malignancy deaths. Recently, its incidence has been increasing in Asian countries such as China and Singapore. 2 Because of its insidious onset, about 70% of patients with ovarian cancer were diagnosed at advanced stage. 3 Although improvement of the quality of cytoreductive surgery as well as development of novel drugs and new chemotherapy regimens for ovarian cancer therapy have been made, 4 most patients relapse, very few achieve a cure and the 5-year survival rate of patients in advanced stage ranges only from 20 to 25%. [4][5][6][7] The pathogenesis of ovarian cancer is believed to be a multistep process that involves multiple genetic changes, including loss of tumor suppressor genes and activation of oncogenes. 8 Recently, we have focused our research on the genetic changes underlying the development and progression of ovarian carcinoma, and several putative candidate oncogenes, such as eIF5-A2 and SEI-1, have been identified and suggested. 9-11 Although the molecular and/or genetic alterations in this neoplasm has been widely studied, to date, the discovery of specific molecular markers that are present in ovarian carcinoma cells, which could serve as reliable clinical/prognostic factors, is still substantially limited.More recently, we have provided evidence ...