Zhang Cong, Xue Guoliang, Bi Jingwang, Geng Ming, Chu Huili, Guan Yaping, Wang Jun, Wang Baocheng
Department of Oncology, General Hospital, Jinan Command of the People's Liberation Army, Shifan Street 25, Tianqiao District, Jinan, 250031, China.
Tumour Biol. 2014 Jan;35(1):73-80. doi: 10.1007/s13277-013-1008-4. Epub 2013 Jul 20.
Esophageal squamous cell carcinoma (ESCC) is one of the most frequent cancers and a leading cause of death from cancer in China. The human ELAV-like protein HuR has been found to contribute to cancer development and progression through stabilizing a group of cellular mRNAs of cancer-related genes. In this study, we investigated the expression of HuR in a cohort of ESCC patients using immunohistochemical staining. HuR detected in the cytoplasm of cancer cells was positive in 46.6% of 58 ESCC specimens; 75.9% of these specimens had nuclear immunoreactivity for HuR. Cytoplasmic HuR expression was higher in cancer tissues compared to 20 matched adjacent noncancerous tissues. A clinicopathological study showed that cytoplasmic HuR expression was positively associated with lymph node metastasis, depth of tumor invasion, and advanced stage, whereas nuclear HuR expression was not correlated with any clinicopathological factors. Patients positive for cytoplasmic HuR expression had a cumulative 5-year survival rate of 25.3%, whereas it was 43.8% for patients negative for cytoplasmic HuR expression. In a multivariate analysis, cytoplasmic HuR expression was an independent prognostic factor, whereas nuclear positivity for HuR was not. Our results indicate that high cytoplasmic HuR expression is associated with positive lymph node metastasis, deep tumor invasion, high stage, and poor survival in ESCC. Thus, HuR is the first mRNA stability protein whose expression is associated with poor survival in esophageal cancer.
食管鳞状细胞癌（ESCC）是中国最常见的癌症之一，也是癌症死亡的主要原因。研究发现，人ELAV样蛋白HuR通过稳定一组癌症相关基因的细胞mRNA，促进癌症的发生和发展。在本研究中，我们采用免疫组织化学染色法，对一组ESCC患者中HuR的表达情况进行了调查。在58例ESCC标本中，46.6%的癌细胞胞质中检测到的HuR呈阳性；这些标本中75.9%的HuR在细胞核中有免疫反应性。与20例配对的癌旁非癌组织相比，癌组织中胞质HuR的表达更高。一项临床病理研究表明，胞质HuR的表达与淋巴结转移、肿瘤浸润深度和晚期呈正相关，而核HuR的表达与任何临床病理因素均无相关性。胞质HuR表达阳性的患者5年累积生存率为25.3%，而胞质HuR表达阴性的患者为43.8%。在多因素分析中，胞质HuR的表达是一个独立的预后因素，而核HuR阳性则不是。我们的结果表明，ESCC中胞质HuR的高表达与阳性淋巴结转移、肿瘤浸润深、分期高及生存率低有关。因此，HuR是首个其表达与食管癌生存率低相关的mRNA稳定性蛋白。
