Periostin as a key molecule defining desmoplastic environment in colorectal cancer
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ORIGINAL ARTICLE
Periostin as a key molecule defining desmoplastic environment in colorectal cancer Takahiro Sueyama 1 Hideki Ueno 1
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Yoshiki Kajiwara 1
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Satsuki Mochizuki 1 & Hideyuki Shimazaki 2 & Eiji Shinto 1 & Kazuo Hase 1 &
Received: 18 March 2020 / Revised: 26 October 2020 / Accepted: 1 November 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Categorizing desmoplastic reaction (DR) based on the histological findings of cancer-associated fibroblasts is shown to be a promising novel method to predict prognosis of patients with colorectal cancer (CRC). Periostin (POSTN) in cancer-associated stroma is reportedly associated with poor clinical outcomes. Immunohistochemical staining with an anti-POSTN antibody was performed in 73 patients with pStage III CRC (cohort 1). In addition, to evaluate mRNA and protein expression levels of POSTN, we analyzed paired normal and invasive cancer frozen specimens by quantitative real-time polymerase chain reaction and western blot analysis in 41 patients (cohort 2). In cohort 1, according to the DR categorization, 18, 22, and 33 patients were classified as immature, intermediate, and mature, respectively. High immunoreactivity of POSTN was observed 100%, 68.2%, and 27.3%, respectively (p < 0.0001). The 5-year relapse-free survival rates were 56.8% and 82.7% in high and low POSTN expression subgroups, respectively (p = 0.015). In cohort 2, the POSTN mRNA and protein levels were significantly higher in the immature stroma as compared to the stroma characterized as other DR patterns. POSTN expression was closely associated with DR categorization. POSTN may be a key molecule that contributes to the malignant potential of CRC. Keywords Periostin . Desmoplastic reaction . Cancer-associated fibroblasts . Colorectal cancer . Polymerase chain reaction . Western blotting
Introduction * Yoshiki Kajiwara [email protected] Satsuki Mochizuki [email protected] Hideyuki Shimazaki [email protected] Eiji Shinto [email protected] Kazuo Hase [email protected] Hideki Ueno [email protected] 1
Department of Surgery, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama 359-8513, Japan
2
Department of Laboratory Medicine, National Defense Medical College, Tokorozawa, Japan
Malignant tumors are composed of many kinds of cells including neoplastic cells, a variety of mesenchymal cells, and extracellular matrix components that comprise the tumor stroma, which is often termed as the tumor microenvironment. Recent basic studies of tumor biology showed that the tumor microenvironment plays a key role in the malignant potential of the tumor through the induction of epithelial-mesenchymal transition (EMT), which is a phenomenon characterized by the ability of epithelial cancer cells to acquire mesenchymal cell properties and increased mobility [1, 2]. Especially, cancerassociated fibroblasts (CAFs), a major component of the tumor stroma, attracted increasing attention due to the contribution to the microenvironmental regulation of tumor metastasis [3, 4
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