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学科主题: 临床医学
题名:
Phosphatidylinositol 3-kinase CB association with preoperative radiotherapy response in rectal adenocarcinoma
作者: Yu, Wei-Dong1; Peng, Yi-Fan2; Pan, Hong-Da2; Wang, Lin2; Li, Kun1,3; Gu, Jin2
关键词: Phosphatidylinositol 3-kinase CB ; Tumor regression grade ; ypT stage ; Disease-free survival ; Therapeutic target ; Rectal cancer ; Preoperative radiotherapy
刊名: WORLD JOURNAL OF GASTROENTEROLOGY
发表日期: 2014-11-21
DOI: 10.3748/wjg.v20.i43.16258
卷: 20, 期:43, 页:16258-16267
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Gastroenterology & Hepatology
研究领域[WOS]: Gastroenterology & Hepatology
关键词[WOS]: COLORECTAL-CANCER ; EXPRESSION PATTERNS ; TUMOR-REGRESSION ; PROGNOSTIC VALUE ; SIGNAL PATHWAY ; CHEMORADIOTHERAPY ; SURVIVAL ; CELLS ; METASTASIS ; INHIBITOR
英文摘要:

AIM: To examine the correlation of phosphatidylinositol 3-kinase (PIK3) CB expression with preoperative radiotherapy response in patients with stage II/III rectal adenocarcinoma.

METHODS: PIK3CB immunoexpression was retrospectively assessed in pretreatment biopsies from 208 patients with clinical stage II/III rectal adenocarcinoma, who underwent radical surgery after 30-Gy/10-fraction preoperative radiotherapy. The relation between PIK3CB expression and tumor regression grade, clinicopathological characteristics, and survival time was statistically analyzed. Western blotting and in vitro clonogenic formation assay were used to detect PIK3CB expression in four colorectal cancer cell lines (HCT116, HT29, LoVo, and LS174T) treated with 6-Gy ionizing radiation. Pharmacological assays were used to evaluate the therapeutic relevance of TGX-221 (a PIK3CB-specific inhibitor) in the four colorectal cancer cell lines.

RESULTS: Immunohistochemical staining indicated that PIK3CB was more abundant in rectal adenocarcinoma tissues with poor response to preoperative radiotherapy. High expression of PIK3CB was closely correlated with tumor height (P < 0.05), ypT stage (P < 0.05), and high-degree tumor regression grade (P < 0.001). High expression of PIK3CB was a potential prognostic factor for local recurrence-free survival (P < 0.05) and metastasis-free survival (P < 0.05). High expression of PIK3CB was also associated with poor therapeutic response and adverse outcomes in rectal adenocarcinoma patients treated with 30-Gy/10-fraction preoperative radiotherapy. In vitro, PIK3CB expression was upregulated in all four colorectal cancer cell lines concurrently treated with 6-Gy ionizing radiation, and the PIK3CB-specific inhibitor TGX-221 effectively inhibited the clonogenic formation of these four colorectal cancer cell lines.

CONCLUSION: PIK3CB is critically involved in response to preoperative radiotherapy and may serve as a novel target for therapeutic intervention. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

语种: 英语
所属项目编号: 30872923 ; RDB2007-47 ; RDK2008-01 ; RDB2011-25
项目资助者: National Natural Science Foundation of China ; Peking University People&prime ; s Hospital Research and Development Fund
WOS记录号: WOS:000346050500034
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63460
Appears in Collections:北京大学第二临床医学院_临床分子生物学研究所_期刊论文

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作者单位: 1.Peking Univ, Inst Clin Mol Biol, Peoples Hosp, Beijing 100044, Peoples R China
2.Peking Univ, Dept Colorectal Surg, Key Lab Carcinogenesis & Translat Res, Canc Hosp & Inst,Minist Educ, Beijing 100142, Peoples R China
3.Pe king Univ, Peoples Hosp, Dept Gastroenterol, Beijing 100044, Peoples R China

Recommended Citation:
Yu, Wei-Dong,Peng, Yi-Fan,Pan, Hong-Da,et al. Phosphatidylinositol 3-kinase CB association with preoperative radiotherapy response in rectal adenocarcinoma[J]. WORLD JOURNAL OF GASTROENTEROLOGY,2014,20(43):16258-16267.
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