Lin Tao-Yan, Chen Yan, Jia Jun-Shuang, Zhou Chen, Lian Mei, Wen Yue-Ting, Li Xiao-Yan, Chen Heng-Wei, Lin Xiao-Lin, Zhang Xiao-Ling, Xiao Sheng-Jun, Sun Yan, Xiao Dong
Guangdong 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.
Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin 541199, People's Republic of China.
Cancer Manag Res. 2019 Jul 24;11:6959-6969. doi: 10.2147/CMAR.S211389. eCollection 2019.
The correlation of cold-inducible RNA-binding protein (Cirbp) expression with clinicopathological features including patient prognosis in nasopharyngeal carcinoma (NPC) was investigated. The expression of Cirbp in NPC cell lines and tissue specimens was examined by qRT-PCR or immunohistochemistry (IHC). 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. Collectively, these findings demonstrate that loss of Cirbp expression is correlated with malignant progression and poor prognosis in NPC.
研究了冷诱导RNA结合蛋白（Cirbp）表达与鼻咽癌（NPC）患者临床病理特征（包括患者预后）之间的相关性。通过qRT-PCR或免疫组织化学（IHC）检测NPC细胞系和组织标本中Cirbp的表达。免疫组织化学（IHC）结果显示，在61例非癌性鼻咽鳞状上皮活检组织中，有61例检测到Cirbp高表达，而在NPC标本中观察到Cirbp表达显著降低。此外，Cirbp蛋白的免疫组织化学分析表明，177例NPC样本的细胞和鼻咽鳞状上皮细胞在细胞核中显示强信号，在细胞质中显示弱信号，而在许多其他癌症中，Cirbp蛋白主要在细胞质中检测到。更重要的是，TNM分类显示，与T1-T2、N0-N1、M0和I-II期肿瘤以及分化型非角化癌（DNKC）相比，在T3-T4、N2-N3、M1和III-IV期NPC活检组织及未分化癌（UDC）中更常观察到Cirbp低表达，这表明Cirbp缺失是NPC晚期病例中的关键分子事件。Kaplan-Meier生存分析表明，Cirbp表达较低的NPC患者总生存时间明显短于Cirbp表达较高的患者。多变量分析表明，Cirbp表达水平是NPC生存的独立预后指标。最后，我们发现NPC活检组织中Cirbp表达与E-钙黏蛋白之间存在显著正相关，Cirbp表达与Ki67标记指数之间存在显著负相关。总之，这些发现表明Cirbp表达缺失与NPC的恶性进展和不良预后相关。
