p53-Altered FBXW7 Expression Determines Poor Prognosis in Gastric Cancer Cases
p53-Altered FBXW7 Expression Determines Poor Prognosis in Gastric Cancer Cases
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DOI：
10.1158/0008-5472.can-08-2846
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发表时间：
2009-05-01
期刊：
影响因子：
11.2
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
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作者：
Yokobori, Takehiko;Mimori, Koshi;Mori, Masaki
与胃癌进展相关的分子靶点尚未被发现。FBXW7是一个由p53转录控制的肿瘤抑制基因，通过c-Myc降解调控细胞周期退出和再进入。很少有研究报道FBXW7在胃癌中表达的临床意义。因此，我们检测了100例胃癌中FBXW7 mRNA的表达，以确定其临床病理意义。FBXW7在原发性胃癌中表达水平低，可导致淋巴结转移（P = 0.0012）、肿瘤大小（P = 0.0003）、预后不良（P = 0.018）等恶性肿瘤的发生。与52例未发生p53突变的胃癌相比，29例发生突变的胃癌患者FBXW7表达水平较低（P = 0.0034），说明p53突变与FBXW7表达有显著关系。此外，我们发现FBXW7低表达和p53突变的胃癌患者与其他亚组相比，预后明显较差（P = 0.0033）。总之，我们在临床胃癌病例中发现p53在FBXW7表达的转录调控中起重要作用，p53和FBXW7均被破坏导致预后不良。[癌症研究2009；69 (9): 3788 - 94)
A molecular target associated with the progression of gastric cancer has not yet been uncovered. FBXW7 is a tumor suppressor gene transcriptionally controlled by p53 that plays a role in the regulation of cell cycle exit and reentry via c-Myc degradation. Few studies have addressed the clinical significance of FBXW7 expression in gastric cancer. Therefore, we examined FBXW7 mRNA expression to determine its clinicopathologic significance in 100 cases of gastric cancer. Low expression levels of FBXW7 in primary gastric cancer contributed to malignant potential, such as lymph node metastasis (P = 0.0012), tumor size (P = 0.0003), and poor prognosis (P = 0.018). In comparison with 52 cases of gastric cancer without the p53 mutation, 29 cases with the mutation exhibited lower expression levels of FBXW7 (P = 0.0034), revealing a significant relationship between p53 mutation and FBXW7 expression. Furthermore, we found that gastric cancer patients who had low FBXW7 expression levels and p53 mutation had a distinctively poor prognosis in comparison with other subgroups (P = 0.0033). In conclusion, we showed a rote for p53 in the transcriptional regulation of FBXW7 expression in clinical gastric cancer cases and showed that disruption of both p53 and FBXW7 contributes to poor prognosis. [Cancer Res 2009;69(9):3788-94]