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人非小细胞肺癌中Hu抗原受体(HuR)和环氧化酶-2(COX-2)的表达:与临床病理参数、肿瘤增殖能力及患者生存的关系

Hu-antigen receptor (HuR) and cyclooxygenase-2 (COX-2) expression in human non-small-cell lung carcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients' survival.

作者信息

Giaginis Constantinos, Alexandrou Paraskevi, Tsoukalas Nikolaos, Sfiniadakis Ioannis, Kavantzas Nikolaos, Agapitos Emmanuel, Patsouris Efstratios, Theocharis Stamatios

机构信息

First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 75 M. Asias str, Goudi, Athens, 11527, Greece.

出版信息

Tumour Biol. 2015 Jan;36(1):315-27. doi: 10.1007/s13277-014-2637-y. Epub 2014 Sep 25.

Abstract

Hu-antigen R (HuR) is considered to play a central role in tumor formation, growth, and metastasis by binding to messenger RNAs (mRNAs) encoding proteins such as cyclooxygenase-2 (COX-2) and inducing their expression via mRNA stabilization and/or altered translation. The present study aimed to evaluate the clinical significance of HuR and COX-2 protein expression in non-small-cell lung carcinoma (NSCLC). HuR and COX-2 expression was assessed immunohistochemically on tissue microarrays of 81 surgically resected NSCLC and was analyzed in relation with clinicopathological characteristics and patients' survival. Enhanced total HuR expression was significantly associated with tumor histological type and presence of lymph node metastases, as well as with increased tumor proliferative capacity and poor patients' outcome (p = 0.039, p = 0.017, p = 0.033, and p = 0.022, respectively). Enhanced COX-2 expression was significantly associated with the presence of lymphovascular invasion and increased tumor proliferative capacity (p = 0.031 and p = 0.023, respectively). Concomitant elevated HuR/COX-2 expression levels were significantly associated with tumor histological type and increased proliferative capacity (p = 0.002 and p = 0.045, respectively). Enhanced total HuR expression, as well as its cytoplasmic localization, was significantly associated with increased COX-2 expression (p = 0.015 and p = 0.001, respectively). The present study supported evidence that HuR may participate in malignant transformation of NSCLC, reinforcing its usefulness as potential therapeutic target in this type of neoplasia.

摘要

Hu抗原R(HuR)被认为通过与编码环氧化酶-2(COX-2)等蛋白质的信使核糖核酸(mRNA)结合,并通过mRNA稳定和/或改变翻译来诱导其表达,从而在肿瘤形成、生长和转移中发挥核心作用。本研究旨在评估HuR和COX-2蛋白表达在非小细胞肺癌(NSCLC)中的临床意义。采用免疫组织化学方法对81例手术切除的NSCLC组织芯片进行HuR和COX-2表达评估,并分析其与临床病理特征及患者生存情况的关系。HuR总表达增强与肿瘤组织学类型、淋巴结转移的存在显著相关,也与肿瘤增殖能力增加和患者预后不良相关(分别为p = 0.039、p = 0.017、p = 0.033和p = 0.022)。COX-2表达增强与淋巴管浸润的存在和肿瘤增殖能力增加显著相关(分别为p = 0.031和p = 0.023)。HuR/COX-2表达水平同时升高与肿瘤组织学类型和增殖能力增加显著相关(分别为p = 0.002和p = 0.045)。HuR总表达增强及其在细胞质中的定位与COX-2表达增加显著相关(分别为p = 0.015和p = 0.001)。本研究支持了HuR可能参与NSCLC恶性转化的证据,强化了其作为这类肿瘤潜在治疗靶点的有用性。

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