Overexpression of Frat1 correlates with malignant phenotype and advanced stage in human non-small cell lung cancer
Overexpression of Frat1 correlates with malignant phenotype and advanced stage in human non-small cell lung cancer
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Frat1 的过度表达与人类非小细胞肺癌的恶性表型和晚期阶段相关
DOI：
10.1007/s00428-011-1135-5
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发表时间：
2011-09-01
期刊：
影响因子：
3.5
通讯作者：
Wang, En-Hua
中科院分区：
文献类型：
--
作者：
Zhang, Yong;Yu, Juan-Han;Wang, En-Hua
据报道，Frat 1在几种人类恶性肿瘤中过表达，包括食管鳞状细胞癌、宫颈癌、乳腺癌和卵巢癌，但Frat 1在肺癌中的作用尚不清楚。本研究旨在探讨Frat 1在肺癌组织中的表达及其与临床病理特征和预后的关系。对137例非小细胞肺癌（NSCLC）组织进行免疫组化染色，并对其中78例进行了临床随访;对30例NSCLC组织和自体配对正常组织进行Western blot和RT-PCR检测蛋白和mRNA表达水平。此外，将Frat 1-siRNA质粒转染肺癌细胞株A549，采用Matrigel侵袭实验研究Frat 1在肺癌细胞侵袭中的作用。结果：免疫组化检测85例（62.04%）非小细胞肺癌组织中Frat 1阳性表达，30例正常肺组织均为阴性。Western blot和RT-PCR检测结果与免疫组化结果一致。Frat 1的表达与肿瘤分化程度、TNM分期、淋巴结转移密切相关（P< 0.05）。Kaplan-Meier生存分析显示，Frat 1阳性表达者的生存期明显短于Frat 1阴性表达者（P< 0.001）。此外，下调Frat 1表达降低了A549细胞系的侵袭能力，进一步支持了Frat 1可能在人类肺癌的致癌、肿瘤侵袭和扩散中起关键作用的观点。
Frat1 has been reported to be overexpressed in several human malignant tumors, including esophageal squamous, cervical, breast, and ovarian carcinoma, but the role of Frat1 in lung cancer is unknown. Our purpose is to investigate the expression of Frat1 and its correlation with clinicopathologic features and prognosis in lung cancer patients. Immunohistochemistry was performed on 137 cases of non-small cell lung cancer (NSCLC), including 78 cases with clinical follow-up, and Western blot and reverse transcription-polymerase chain reaction (RT-PCR) assays were performed to detect the protein and mRNA expression levels in 30 NSCLC and autologous matched normal tissues. In addition, lung cancer cell line A549 was transfected with Frat1-siRNA plasmids and Matrigel invasive assay was carried out to study the function of Frat1 in cancer cell invasiveness. The results showed that Frat1 was expressed in 85 (62.04%) cases of NSCLC by immunohistochemistry, while all 30 specimens of normal lung tissues were negative. Western blot and RT-PCR results for Frat1 mRNA were in agreement with immunohistochemical findings. Of interest, the expression of Frat1 was strongly correlated with tumor differentiation, TNM stage, and lymph node metastasis (P< 0.05). The Kaplan–Meier survival analysis demonstrated that the cases with Frat1 expression had significantly shorter survival than those without Frat1 (P< 0.001). In addition, down-regulation of Frat1 expression reduced the invasive ability in the A549 cell line, further supporting the idea that Frat1 may play a crucial role in carcinogenesis, tumor invasiveness and dissemination in human lung cancer.