The molecular role of Fra-1 and its prognostic significance in human esophageal squamous cell carcinoma
The molecular role of Fra-1 and its prognostic significance in human esophageal squamous cell carcinoma
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DOI：
10.1002/cncr.26652
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发表时间：
2012-07-01
期刊：
影响因子：
6.2
通讯作者：
Matsubara, Hisahiro
中科院分区：
文献类型：
--
作者：
Usui, Akihiro;Hoshino, Isamu;Matsubara, Hisahiro
背景：fr -1 （Fos相关抗原1）的表达参与肿瘤的进展和侵袭，其基因消融可抑制人肿瘤细胞的侵袭表型。作者探讨了Fra-1在食管鳞状细胞癌（ESCC）中表达的意义，并研究其下调对食管鳞状细胞癌细胞增殖、运动和侵袭的影响。方法：对164例ESCC患者的手术标本进行评价。比较原发肿瘤及转移淋巴结中Fra-1表达的各种临床病理特征，并分析总生存率。研究了Fra-1免疫反应率和强度。通过Fra-1在人ESCC细胞株中的下调来评估其分子作用。结果：127例ESCC患者（77.4%）Fra-1表达阳性。免疫反应性局限于ESCC肿瘤边缘区域。Fra-1阳性表达与肿瘤深度、淋巴结转移、分期、浸润生长方式相关。存在和不存在Fra-1的肿瘤的生存率有显著差异，Fra-1阳性表达是与预后不良相关的独立因素。与fr -1阴性表达的患者相比，fr -1阳性表达的转移性淋巴结患者的生存率降低。下调Fra-1表达后，观察到细胞增殖、活力和侵袭性明显降低。结论：本研究表明，Fra-1阳性的ESCC患者预后较差。研究结果还表明，Fra-1调控可能在ESCC的进展中发挥重要作用。2011年癌症。(c) 2011年美国癌症协会。
BACKGROUND: The expression of Fra-1 (Fos related antigen 1) involves tumor progression and invasion, and its gene ablation could suppress the invasive phenotypes of human tumor cells. The authors investigated the significance of Fra-1 expression in esophageal squamous cell carcinoma (ESCC) and studied the effect of its down-regulation on cell proliferation, motility, and invasion. METHODS: Surgical specimens from 164 patients with ESCC were evaluated. Fra-1 expression in the primary tumor along with metastatic lymph nodes was compared among various clinicopathological characteristics, and overall survival was analyzed. The rate and intensity of Fra-1 immunoreactivity were also investigated. The molecular role of Fra-1 was assessed by its down-regulation in human ESCC cell lines. RESULTS: Fra-1 expression was positive in 127 (77.4%) ESCC patients. Immunoreactivity was localized to the marginal areas of the ESCC tumors. Positive Fra-1 expression correlated with depth of tumor, lymph node metastasis, stage, and infiltrative growth pattern. A significant difference was seen in the survival between tumors with and without Fra-1, and positive Fra-1 expression was revealed to be an independent factor related to poor prognosis. Patients with metastatic lymph nodes with positive Fra-1 expression presented decreased survival compared with negative Fra-1 expression. After the down-regulation of Fra-1 expression, a significant decrease in cell proliferation, motility, and invasion was observed. CONCLUSIONS: This study demonstrated ESCC patients positive for Fra-1 to be associated with poor prognosis. The findings also suggest that Fra-1 regulation may play an important role in the progression of ESCC. Cancer 2011. (c) 2011 American Cancer Society.