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.
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 cancerpatients. After chemoradiotherapy, 64 of 86 (74.4 %) locally advanced rectal cancerpatients 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 cancerpatients who may have a poor response risk to preoperative fluoropyrimidine-based chemoradiotherapy.
Authors: Jose G Guillem; David B Chessin; Alfred M Cohen; Jinru Shia; Madhu Mazumdar; Warren Enker; Philip B Paty; Martin R Weiser; David Klimstra; Leonard Saltz; Bruce D Minsky; W Douglas Wong Journal: Ann Surg Date: 2005-05 Impact factor: 12.969
Authors: Eva Dreussi; Salvatore Pucciarelli; Antonino De Paoli; Jerry Polesel; Vincenzo Canzonieri; Marco Agostini; Maria Luisa Friso; Claudio Belluco; Angela Buonadonna; Sara Lonardi; Chiara Zanusso; Elena De Mattia; Giuseppe Toffoli; Erika Cecchin Journal: Oncotarget Date: 2016-04-12