Periostin from Tumor Stromal Cells Might Be Associated with Malignant Progression of Colorectal Cancer Via Smad2/3

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2025 Feb 13

PMID 39941916

Authors

Canfeng Fan

Qiang Wang

Saki Kanei

Kyoka Kawabata

Hinano Nishikubo

Rika Aoyama

Zhonglin Zhu

Daiki Imanishi

Takashi Sakuma

Koji Maruo

Gen Tsujio

Yurie Yamamoto

Tatsunari Fukuoka

Masakazu Yashiro

Affiliations

Soon will be listed here.

Abstract

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. 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. 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 ( < 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. 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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