Department of Pathology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, South Korea.
Mod Pathol. 2011 Oct;24(10):1336-47. doi: 10.1038/modpathol.2011.90. Epub 2011 May 13.
Hu antigen R (HuR) is a member of the human family of embryonic-lethal, abnormal vision-like proteins, which serves as an mRNA-binding protein. In the cytoplasm, HuR can stabilize the mRNA of cyclooxygenase-2 (COX-2), an enzyme that catalyses the synthesis of prostaglandins and is associated with promotion of carcinogenesis and tumor cell resistance to apoptosis. Intracellular (cytoplasmic and nuclear) localization of survivin has a prognostic significance as an apoptosis inhibitor and a regulator of cell division in tumors. Patients with 151 squamous cell carcinomas and 93 adenocarcinomas underwent lobectomy or pneumonectomy with hilar and mediastinal lymph node sampling. Paraffin-embedded tumor sections were retrieved for evaluation of nuclear and cytoplasmic staining of survivin and HuR, and cytoplasmic staining of COX-2. In squamous cell carcinomas, COX-2 expression was correlated with a difference of survivin (cytoplasmic-nuclear; P=0.004), cytoplasmic HuR (P=0.018), total HuR (cytoplasmic+nuclear; P=0.009), and difference of HuR (P=0.020). COX-2 was inversely correlated with nuclear survivin (P=0.006). In a univariate analysis by log-rank test, survival was associated with cytoplasmic survivin (adenocarcinoma, P<0.001; squamous cell carcinoma, P=0.005), difference of survivin (adenocarcinoma, P<0.001; squamous cell carcinoma, P=0.014), and COX-2 (squamous cell carcinoma, P=0.001). Survival was inversely associated with nuclear survivin (adenocarcinoma, P=0.006, squamous cell carcinoma, P=0.014). In a multivariate survival analysis, cytoplasmic survivin (adenocarcinoma, P=0.002; squamous cell carcinoma, P=0.015) and COX-2 (squamous cell carcinoma, P=0.020) were determined as independent prognostic factors. Cytoplasmic HuR expression is associated with COX-2 expression in squamous cell carcinomas. The expression of COX-2 in squamous cell carcinomas, and cytoplasmic survivin in adenocarcinomas and squamous cell carcinomas could be useful independent prognostic markers.
Hu 抗原 R（HuR）是人类胚胎致死性、异常视觉样蛋白家族的成员，作为一种 mRNA 结合蛋白。在细胞质中，HuR 可以稳定环氧化酶-2（COX-2）的 mRNA，COX-2 是一种催化前列腺素合成的酶，与促进致癌作用和肿瘤细胞对凋亡的抵抗力有关。存活素的细胞内（细胞质和核）定位作为凋亡抑制剂和肿瘤细胞分裂的调节剂具有预后意义。对 151 例鳞状细胞癌和 93 例腺癌患者进行了肺叶切除术或全肺切除术，并进行了肺门和纵隔淋巴结取样。检索石蜡包埋的肿瘤切片，以评估核和细胞质中存活素和 HuR 的染色，以及细胞质中 COX-2 的染色。在鳞状细胞癌中，COX-2 表达与存活素（细胞质-核；P=0.004）、细胞质 HuR（P=0.018）、总 HuR（细胞质+核；P=0.009）和 HuR 差异（P=0.020）有关。COX-2 与核存活素呈负相关（P=0.006）。通过对数秩检验的单因素分析，生存与细胞质存活素（腺癌，P<0.001；鳞状细胞癌，P=0.005）、存活素差异（腺癌，P<0.001；鳞状细胞癌，P=0.014）和 COX-2（鳞状细胞癌，P=0.001）有关。生存与核存活素呈负相关（腺癌，P=0.006，鳞状细胞癌，P=0.014）。在多因素生存分析中，细胞质存活素（腺癌，P=0.002；鳞状细胞癌，P=0.015）和 COX-2（鳞状细胞癌，P=0.020）被确定为独立的预后因素。在鳞状细胞癌中，细胞质 HuR 表达与 COX-2 表达相关。COX-2 在鳞状细胞癌中的表达，以及在腺癌和鳞状细胞癌中的细胞质存活素，可以作为有用的独立预后标志物。
