title: Phosphatidylinositol 3-kinase CB association with preoperative radiotherapy response in rectal adenocarcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  PIK3CB is critically involved in response to preoperative radiotherapy and may serve as a novel target for therapeutic intervention.
authors.affiliation: Wei-Dong Yu, Kun Li, Institute of Clinical Molecular Biology, People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Yu
authors.affiliation: Wei-Dong Yu, Kun Li, Institute of Clinical Molecular Biology, People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Peng
authors.affiliation: Wei-Dong Yu, Kun Li, Institute of Clinical Molecular Biology, People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Hong-Da
authors.initials: HD
authors.lastname: Pan
authors.affiliation: Wei-Dong Yu, Kun Li, Institute of Clinical Molecular Biology, People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Wei-Dong Yu, Kun Li, Institute of Clinical Molecular Biology, People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.affiliation: Wei-Dong Yu, Kun Li, Institute of Clinical Molecular Biology, People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gu
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; C497132:PIK3CB protein, human
keywords: Disease-free survival; Phosphatidylinositol 3-kinase CB; Preoperative radiotherapy; Rectal cancer; Therapeutic target; Tumor regression grade; ypT stage