Ribonucleotide reductase M2 subunit expression and prognostic value in nasopharyngeal carcinoma

Han,Ping; Lin,Zhi-Rui; Xu,Li-Hua; Zhong,Qian; Zhu,Xiao-Fen; Liang,Fa-Ya; Cai,Qian; Huang,Xiao-Ming; Zeng,Mu-Sheng

doi:10.3892/mmr.2015.3360

Ribonucleotide reductase M2 subunit expression and prognostic value in nasopharyngeal carcinoma

Authors:
- Ping Han
- Zhi-Rui Lin
- Li-Hua Xu
- Qian Zhong
- Xiao-Fen Zhu
- Fa-Ya Liang
- Qian Cai
- Xiao-Ming Huang
- Mu-Sheng Zeng
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Affiliations: Department of Otolaryngology-Head and Neck Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China, Department of Otolaryngology-Head and Neck Surgery, Huizhou First Hospital, Huizhou, Guangdong 516000, P.R. China
Published online on: February 16, 2015 https://doi.org/10.3892/mmr.2015.3360
Pages: 401-409

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Abstract

The ribonucleotide reductase M2 subunit (RRM2) modulates the enzymatic activity of ribonucleotide reductase, and is involved in tumor progression. Recently, high levels of RRM2 expression were reported to correlate with poor survival outcomes in patients with colorectal and bladder cancer. However, changes in RRM2 expression in nasopharyngeal carcinoma (NPC), and its effect on the prognosis of this disease remain unknown. The aim of the present study was to analyze the expression of RRM2 in NPC cell lines, and to identify whether RRM2 may serve as a biomarker with which to assess the prognosis of NPC. The present study found that RRM2 expression was higher in NPC cell lines and tissue samples than in noncancerous nasopharyngeal epithelial cell lines and noncancerous tissues, as shown by reverse transcription‑quantitative polymerase chain reaction analysis, western blotting and immunohistochemistry staining. Kaplan‑Meier survival analysis demonstrated that patients with higher RRM2 expression levels had poorer disease‑free survival outcomes than those with lower expression levels of RRM2. Univariate analysis showed that a lower survival rate was significantly associated with high RRM2 expression levels [hazard ratio (HR), 6.424; 95% confidence interval (CI), 2.381‑17.333; P<0.001]. Multivariate analysis indicated that RRM2 expression is an independent prognostic factor for patients with NPC (HR, 3.461; 95 % CI, 1.204‑9.949; P=0.021). Overexpression of RRM2 led to increased cell proliferation, colony formation, migration and invasion in vivo. These results suggest that high levels of RRM2 expression may be a useful predictor for survival in patients with NPC and may serve as a novel prognostic indicator for these individuals.

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