Related Experiment Video
Updated: Apr 19, 2026
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Relationships between SMAD3 expression and preoperative fluoropyrimidine-based chemoradiotherapy response in locally
Ming-Yii Huang1, Chih-Hung Lin, Chun-Ming Huang
1Department of Radiation Oncology, Cancer Center, Kaohsiung Medical University Hospital, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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.
Insights
Phosphorylated SMAD3 overexpression in locally advanced rectal cancer predicts poor response to chemoradiotherapy and worse survival. Identifying this biomarker pre-treatment can guide patient management for better outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Transforming growth factor-beta (TGF-β) signaling is crucial in cancer, mediated by SMAD proteins.
- SMAD3 accumulates in the nucleus, regulating TGF-β target genes.
- The role of TGF-β1, SMAD3, and phosphorylated SMAD3 in locally advanced rectal cancer (LARC) post-chemoradiotherapy is not fully understood.
Purpose of the Study:
- To investigate the expression of TGF-β1, SMAD3, and phosphorylated SMAD3 in LARC patients.
- To correlate these expressions with response to preoperative fluoropyrimidine-based chemoradiotherapy.
- To assess the prognostic value of these markers for treatment outcomes and survival.
Main Methods:
- Immunohistochemistry was used to analyze TGF-β1, SMAD3, and phosphorylated SMAD3 expression in pre-treatment tumor tissues from 86 LARC patients.
- Patient response was evaluated based on pathological tumor regression grades post-chemoradiotherapy.
Main Results:
- Phosphorylated SMAD3 overexpression was significantly associated with poor response to chemoradiotherapy (P=0.015).
- Poor response to chemoradiotherapy independently predicted postoperative relapse (P=0.021).
- Patients with phosphorylated SMAD3 overexpression exhibited worse disease-free survival (P=0.023).
Conclusions:
- Pre-treatment assessment of phosphorylated SMAD3 overexpression can identify LARC patients at high risk for poor response to chemoradiotherapy.
- This biomarker may aid in personalized treatment strategies for LARC.
- Further research can explore therapeutic targeting of the TGF-β/SMAD3 pathway in rectal cancer.
