|Phosphatidylinositol 3-kinase CB association with preoperative radiotherapy response in rectal adenocarcinoma|
|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|
|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|
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.
|项目编号||30872923 ; RDB2007-47 ; RDK2008-01 ; RDB2011-25|
|资助机构||National Natural Science Foundation of China ; Peking University People&prime ; s Hospital Research and Development Fund|
|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
|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.|
|APA||Yu, Wei-Dong,Peng, Yi-Fan,Pan, Hong-Da,Wang, Lin,Li, Kun,&Gu, Jin.(2014).Phosphatidylinositol 3-kinase CB association with preoperative radiotherapy response in rectal adenocarcinoma.WORLD JOURNAL OF GASTROENTEROLOGY,20(43),16258-16267.|
|MLA||Yu, Wei-Dong,et al."Phosphatidylinositol 3-kinase CB association with preoperative radiotherapy response in rectal adenocarcinoma".WORLD JOURNAL OF GASTROENTEROLOGY 20.43(2014):16258-16267.|
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