Clinicopathologic significance of CXCR4 and Nrf2 in colorectal cancer.
Clinicopathologic significance of CXCR4 and Nrf2 in colorectal cancer.
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CXCR4 和 Nrf2 在结直肠癌中的临床病理意义。
DOI：
10.7555/jbr.27.20130069
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发表时间：
2013-07
影响因子：
2.3
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Hu T;Yao Y;Yu S;Guo H;Han L;Wang W;Tian T;Hao Y;Liu Z;Nan K;Wang S
在各种类型的人类癌症中，CXCR4和Nrf2信号通路在细胞应激反应中异常激活。在本研究中，我们检测了CXCR4和Nrf2在结直肠癌（CRC）组织标本中的表达，并探讨了它们与患者临床病理特征的相关性。我们采用免疫组织化学和实时荧光定量PCR检测了76例结直肠癌组织标本和配对正常组织标本中CXCR4和Nrf2的表达。我们发现CRC组织标本中CXCR4蛋白和mRNA转录水平明显高于配对正常组织，而CRC组织中Nrf2蛋白和mRNA的表达高于远端非癌组织。CXCR4高表达与低分化（P = 0.031）、晚期肿瘤-淋巴结-转移（TNM）分期（P = 0.019）、淋巴结转移（P = 0.007）和远处转移（P = 0.018）呈正相关。而Nrf2蛋白的表达与肿瘤大小（P = 0.049）、TNM分期（P = 0.013）、淋巴结转移（P = 0.016）和远处转移（P = 0.023）呈正相关。此外，在结直肠癌组织中，CXCR4和Nrf2的表达有很强的相关性，表明Nrf2的高表达可能导致CXCR4过表达。此外，CXCR4和Nrf2联合表达与淋巴结转移和远处转移密切相关（P = 0.003）。此外，我们发现CXCR4和Nrf2联合高表达与淋巴结转移和远处转移的相关性比任何单一分子都强。本研究提示CXCR4和Nrf2的异常表达参与了CRC的进展。
The CXCR4 and Nrf2 signaling pathways are abnormally activated in response to cellular stress in various types of human cancers. In this study, we examined the expression of CXCR4 and Nrf2 in colorectal cancer (CRC) tissue specimens and investigated their correlation with patient clinicopathologic characteristics. We determined CXCR4 and Nrf2 expression in 76 CRC tissue specimens and paired normal tissue specimens by immunohistochemistry and real-time PCR. We found that the protein and mRNA transcript levels of CXCR4 were significantly higher in CRC tissue specimens than in paired normal tissues, while the expressions of Nrf2 protein and mRNA were increased in CRC tissues compared to distant non-cancerous tissues. High expression level of CXCR4 was positively correlated with poorly differentiated (P = 0.031), more advanced tumor-node-metastasis (TNM) stage (P = 0.019), lymph node metastasis (P = 0.007) and distant metastasis (P = 0.018). However, the expression of Nrf2 protein was positively correlated with larger tumor size (P = 0.049), more advanced TNM stage (P = 0.013), lymph node metastasis (P = 0.016) and distant metastasis (P = 0.023). Moreover, there was a strong relationship between CXCR4 and Nrf2 expression in CRC tissues, indicating that high Nrf2 expression may contribute to CXCR4 overexpression. In addition, combined expression of CXCR4 and Nrf2 strongly correlated with lymph node metastasis and distant metastasis (P = 0.003). Furthermore, we found that combined high expression of CXCR4 and Nrf2 had stronger correlation with lymph node metastasis and distant metastasis than any single molecule did. This study indicated that the abnormal expression of CXCR4 and Nrf2 contributed to the progression of CRC.