Cancer Management and Research (Jul 2019)
Loss of Cirbp expression is correlated with the malignant progression and poor prognosis in nasopharyngeal carcinoma
Abstract
Tao-Yan Lin,1,* Yan Chen,1,* Jun-Shuang Jia,1,* Chen Zhou,2 Mei Lian,3 Yue-Ting Wen,1 Xiao-Yan Li,3 Heng-Wei Chen,3 Xiao-Lin Lin,1 Xiao-Ling Zhang,4 Sheng-Jun Xiao,2 Yan Sun,5 Dong Xiao1,31Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin 541199, People’s Republic of China; 3Institute of Comparative Medicine and Laboratory Animal Center, Southern Medical University, Guangzhou 510515, People’s Republic of China; 4Department of Physiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin 541004, People’s Republic of China; 5Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China*These authors contributed equally to this workPurpose: The correlation of cold-inducible RNA-binding protein (Cirbp) expression with clinicopathological features including patient prognosis in nasopharyngeal carcinoma (NPC) was investigated.Methods: The expression of Cirbp in NPC cell lines and tissue specimens was examined by qRT-PCR or immunohistochemistry (IHC).Results: Immunohistochemistry (IHC) results showed that high Cirbp expression was detected in 61 of 61 non-cancerous nasopharyngeal squamous epithelial biopsies, whereas the significantly reduced expression of Cirbp was observed in NPC specimens. In addition, IHC assay for Cirbp protein illustrated that the cells of 177 NPC samples and nasopharyngeal squamous epithlial cells displayed strong signals in nuclei and faint signals in cytoplasm, whereas Cirbp protein is mainly detected in the cell’s cytoplasm in many other cancers. More importantly, TNM classification displayed that the low expression of Cirbp was more frequently observed in T3-T4, N2-N3, M1 and III-IV NPC biopsies, and undifferentiated carcinoma (UDC) than T1-T2, N0-N1, M0 and I-II tumors, and differentiated nonkeratinizing carcinoma (DNKC), suggesting that Cirbp loss is a key molecular event in advanced cases of NPC. Kaplan–Meier survival analysis indicated that NPC patients showing lower Cirbp expression had a significantly shorter overall survival time than those with high Cirbp expression. Multivariate analysis suggested that the level of Cirbp expression was an independent prognostic indicator for NPC survival. Finally, we revealed a significant positive association between Cirbp expression and E-cadherin, and a notable negative correlation between Cirbp expression and Ki67 labeling index in NPC biopsies.Conclusion: Collectively, these findings demonstrate that loss of Cirbp expression is correlated with malignant progression and poor prognosis in NPC.Keywords: cirbp, nasopharyngeal carcinoma; NPC, TNM stage, prognosis, E-cadherin, Ki67