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Let-7 Expression Is a Significant Determinant of Response to Chemotherapy through the Regulation of IL-6/STAT3 Pathway in Esophageal Squamous Cell Carcinoma

icecream 添加于 2012-10-14 10:57 | 991 次阅读 | 0 个评论

作者
Sugimura K, Miyata H, Tanaka K, Hamano R, Takahashi T, Kurokawa Y, Yamasaki M, Nakajima K, Takiguchi S, Mori M, Doki Y
摘要
PURPOSE: Cisplatin-based chemotherapy is widely used for esophageal cancer, sometimes in combination with surgery/radiotherapy, but poor response to chemotherapy is not uncommon. The aim of this study was to examine whether miRNA expression is useful to predict the response to chemotherapy in patients with esophageal cancer. EXPERIMENTAL DESIGN: Using pretreatment biopsy samples from 98 patients with esophageal cancer who received preoperative chemotherapy, we measured the expression level of several miRNAs whose expression was altered in cisplatin-resistant esophageal cancer cell lines compared with those parent cell lines and examined the relationship between the miRNA expression and response to chemotherapy. In vitro assays were conducted to clarify the mechanism of miRNA-induced changes in chemosensitivity. RESULTS: The expression levels of 15 miRNAs were altered in cisplatin-resistant cells. Of these, low expression of let-7b and let-7c in before-treatment biopsies from 74 patients of the training set correlated significantly with poor response to chemotherapy, both clinically and histopathologically. Low expression of let-7c also correlated with poor prognosis (P = 0.032). The relationship between let-7b and let-7c expression and response to chemotherapy was confirmed in the other 24 patients of the validation set. In in vitro assay, transfection of let-7c restored sensitivity to cisplatin and increased rate of apoptosis after exposure to cisplatin. Let-7c directly repressed cisplatin-activated interleukin (IL)-6/STAT3 prosurvival pathway. CONCLUSIONS: Let-7 expression in esophageal cancer can be potentially used to predict the response to cisplatin-based chemotherapy. Let-7 modulates the chemosensitivity to cisplatin through the regulation of IL-6/STAT3 pathway in esophageal cancer. Clin Cancer Res; 18(18); 5144-53. (c)2012 AACR.
详细资料
- 文献种类: Journal Article
- 期刊名称: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
- 期刊缩写: Clin Cancer Res
- 期卷页: 2012年第18卷第18期 5144-5153页
- 地址: Authors' Affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamada oka, Suita, Osaka, Japan
- ISBN: 1078-0432
学科领域生物医药 » 预防卫生学
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