Key result
High stromal periostin expression independently predicts worse overall survival in colorectal cancer.
Why the study?
The clinicopathologic significance of periostin and Smad2/3 expression in colorectal cancer, particularly within the tumor microenvironment, remained to be clarified.
Does periostin and Smad2/3 expression in cancer-associated fibroblasts predict poorer overall survival and malignant clinicopathologic progression in patients with colorectal cancer undergoing colectomy?
Cohort (n=351)
Immunostaining levels evaluated by two independent observers unaware of clinical data and outcomes
No
Does periostin and Smad2/3 expression in cancer-associated fibroblasts predict poorer overall survival and malignant clinicopathologic progression in patients with colorectal cancer undergoing colectomy?
Periostin expression in cancer-associated fibroblasts correlates closely with Smad2/3 signaling and serves as an independent predictor of poor overall survival and advanced malignant features in colorectal cancer.
Answers are grounded in this paper and cite their sources.
May inform colorectal cancer prognosis after colectomy; leaves open whether periostin targeting alters outcomes.
Background/Objectives: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been reported to be closely associated with tumor progression in various types of cancer, including colorectal cancer (CRC). Periostin, a matricellular protein, was reported to be expressed on both cancer cells and surrounding tumor stromal cells, such as CAFs, and is regulated by Smad2/3 signaling. In this study, we aimed to clarify the clinicopathologic significance of periostin and Smad2/3 expression in CRC, with a particular focus on the tumor microenvironment. Methods: A total of 351 CRC patients were enrolled according to the inclusion and exclusion criteria. The expressions of periostin and Smad2/3 in the tumor specimens were examined by immunohistochemistry. Results: Periostin expression of CAFs and cancer cells in the 351 CRC cases was observed at 36.8% and 0.6%, respectively. Smad2/3 expression of CAFs and cancer cells was observed in 41.0% and 90.0%, respectively. In CAFs, high periostin expression was significantly correlated with high Smad2/3 expression, increased invasion depth, lymph node metastasis, venous invasion, advanced disease stage, and a higher rate of relapse. The prognoses of patients with periostin-positive CAFs were significantly poorer than those with periostin-negative CAFs (p < 0.001). The survival outcomes of stage 3 CRC patients with co-expression of periostin and Smad2/3 were significantly worse compared to those with stage 2 CRC. In the stage 3 group, multivariate analysis revealed that periostin was an independent prognostic factor, while univariate analysis showed that both periostin and Smad2/3 were significantly correlated with poor survival. Conclusions: These findings suggest that periostin is expressed mainly in CAFs in CRC and is correlated with Smad2/3 expression in CAFs. Periostin from CAFs might be associated with the malignant progression of CRC via Smad2/3 signaling.
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Fan et al. (2025) conducted a cohort in Colorectal cancer (n=351). Periostin and Smad2/3 expression in cancer-associated fibroblasts (CAFs) vs. Periostin-negative and/or Smad2/3-negative CAFs was evaluated on 5-year overall survival (p=<0.001). Periostin expression in cancer-associated fibroblasts was observed in 36.8% of colorectal cancer patients and independently predicted poorer overall survival in multivariate analysis.
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