• Ying-Fang Su, Tzu-Fan Wu, Jiunn-Liang Ko, Hsiu-Ting Tsai, Yi-Torng Tee, Ming-Hsien Chien, Chi-Hung Chou, Wea-Lung Lin, Hui-Ying Low, Ming-Yung Chou, Shun-Fa Yang, and Po-Hui Wang.
• Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Stomatology, Chung Shan Medical University Hospital, Taichung, Taiwan.
• Plos One. 2014 Jan 1; 9 (3): e91644.

BackgroundTo investigate the implication of ribonucleotide reductase M2 (RRM2) in the carcinogenesis of uterine cervix and its relationship with clinicopathological characteristics and prognosis of cancer patients.Methodology And Principal FindingsThe impact of RRM2 on cell viability was investigated in SiHa cervical cancer cells after RRM2 knockdown and the addition of cisplatin, which induces inter- and intra-strand DNA crosslinks. RRM2 immunoreactivity was evaluated by semi-quantitative H score among 29 normal, 30 low-grade dysplasia, 30 high-grade dysplasia and 103 invasive cancer tissue specimens of the uterine cervix, using tissue microarrays. RRM2 was then correlated with the clinicopathological variables of cervical cancer and patient survival. A greater toxic effect on cell viability using cisplatin was reflected by the greater reduction in RRM2 protein expression in SiHa cells. The RRM2 expression in cancer tissues was higher than that in high-grade dysplasia, low-grade dysplasia or normal cervical tissues. RRM2 upregulation was correlated with deep stromal invasion, large tumors and parametrial invasion and predicted poor survival.ConclusionsRRM2 is a new molecular marker for the diagnosis and clinical outcomes of cervical cancer. It is involved in cervical carcinogenesis and predicts poor survival, and may be a potential therapeutic target including in cisplatin treatment.

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