title: Relationships between SMAD3 expression and preoperative fluoropyrimidine-based chemoradiotherapy response in locally advanced rectal cancer patients.
abstract: BACKGROUND
  SMAD3, which is accumulated in the nucleus, transcriptionally regulates TGF-β target genes, playing a significant role in mediating the activities of TGF-β. In this study, we assessed the roles of TGF-β1, SMAD3, and phosphorylated SMAD3 expressions in patients with locally advanced rectal cancer following preoperative fluoropyrimidine-based chemoradiotherapy.
  
  
  METHODS
  Using immunohistochemistry, we examined TGF-β1, SMAD3, and phosphorylated SMAD3 expressions in pre-chemoradiotherapy cancer tissues from 86 locally advanced rectal cancer patients. After chemoradiotherapy, 64 of 86 (74.4 %) locally advanced rectal cancer patients were classified as responders (pathological tumor regression grades of 2-4).
  
  
  RESULTS
  A multivariate analysis showed that phosphorylated SMAD3 overexpression correlated to poor preoperative chemoradiotherapy responses (P = 0.015; OR 7.218; 95 % CI 1.479-35.229). Furthermore, a poor response (pathological tumor regression grades of 0-1) was an independent predictor of postoperative relapse (P = 0.021; OR 5.452; 95 % CI 1.286-23.113). Additionally, patients with phosphorylated SMAD3 overexpression were found to have a worse disease-free survival (P = 0.023).
  
  
  CONCLUSIONS
  Our data suggested that analyzing pre-chemoradiotherapy tumors for phosphorylated SMAD3 overexpression would assist physicians in identifying locally advanced rectal cancer patients who may have a poor response risk to preoperative fluoropyrimidine-based chemoradiotherapy.
authors.affiliation: Department of Radiation Oncology, Cancer Center, Kaohsiung Medical University Hospital, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Yii
authors.initials: MY
authors.lastname: Huang
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Huang
authors.forename: Hsiang-Lin
authors.initials: HL
authors.lastname: Tsai
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Huang
authors.forename: Yung-Sung
authors.initials: YS
authors.lastname: Yeh
authors.forename: Chee-Yin
authors.initials: CY
authors.lastname: Chai
authors.forename: Jaw-Yuan
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D059186:Chemoradiotherapy, Adjuvant; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D010766:Phosphorylation; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000628:therapy*; D051900:Smad3 Protein / Q000378:metabolism*; D015996:Survival Rate; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D002955:Leucovorin; D005472:Fluorouracil