Loss of Cirbp expression is correlated with the malignant progression and poor prognosis in nasopharyngeal carcinoma

Abstract

Purpose: 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

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 81872209, 81672689, 81372896 and 81172587, to D Xiao; Grant No. 81600086 and 81770100, to Y Sun; Grant No. 81600488 and 81870602, to XL Lin; Grant No. 81702778, to JS Jia; Grant No. 81560441 and 81760491, to SJ Xiao), the Science and Technology Planning Project of Guangdong Province of China (Grant No. 2017A030303018, to JS Jia) and the Medical Scientific Research Foundation of Guangdong Province of China (Grant No. A2017420, to JS Jia).

Abbreviation list

Cirbp, cold-inducible RNA-binding protein; DNKC, differentiated non-keratinizing carcinoma; EMT, epithelial-mesenchymal transition; IHC, immunohistochemistry; NPC, nasopharyngeal carcinoma; TMA, tissue microarray; UDC, undifferentiated carcinoma.

Author contributions

D Xiao, Y Sun and SJ Xiao conceived and designed the study; TY Lin, SJ Xiao, Y Chen, JS Jia, C Zhou, M Lian, YT Wen, XY Li and HW Chen performed the experiments; D Xiao, SJ Xiao and TY Lin analyzed the data; XL Lin and XL Zhang contributed essential reagents or tools; D Xiao, TY Lin and SJ Xiao wrote the paper. All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.