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01-12-2019 | Translational Research and Biomarkers

Vimentin Expression in Tumor Microenvironment Predicts Survival in Pancreatic Ductal Adenocarcinoma: Heterogeneity in Fibroblast Population

Authors: Hiromitsu Maehira, MD, Toru Miyake, MD, PhD, Hiroya Iida, MD, PhD, Aya Tokuda, MD, Haruki Mori, MD, Daiki Yasukawa, MD, Ken-ichi Mukaisho, MD, PhD, Tomoharu Shimizu, MD, PhD, Masaji Tani, MD, PhD

Published in: Annals of Surgical Oncology | Issue 13/2019

Abstract

Background

The tumor microenvironment, including cancer-associated fibroblasts (CAFs), plays various clinical roles in cancer growth. CAFs are a heterogeneous population and express a variety of mesenchymal markers. However, the clinical roles for CAFs expressing different markers in pancreatic ductal adenocarcinoma (PDAC) remain unknown.

Methods

We reviewed 67 resected PDAC patients who had not received preoperative therapy. Each primary tumor was analyzed for vimentin and α-smooth muscle actin (α-SMA) expression by immunohistochemical and dual immunofluorescence staining.

Results

There was no correlation between the percentage of cells expressing vimentin and α-SMA in the tumor stroma (Pearson’s correlation coefficient: r = 0.171). Higher vimentin expression (p = 0.018) was associated with significantly shorter overall survival in PDAC patients. Using dual immunofluorescence staining, vimentin-positive CAFs were divided into two subpopulations: co-expression of α-SMA, and no co-expression of α-SMA. In PDAC, the level of co-expression had no effect on survival using univariate analysis (median survival time, 33.3 months for low co-expression vs. 18.2 months for high co-expression; log-rank, p = 0.143). However, multivariate analysis clarified that CAFs expressing vimentin alone was an independent predictor of poor survival (p = 0.014; hazard ratio, 2.305; 95% confidence interval, 1.181–4.497).

Conclusions

Vimentin-positive CAFs without co-expression of α-SMA were associated with poor survival in PDAC, and CAFs possessed molecular and functional heterogeneity in this disease.

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Title: Vimentin Expression in Tumor Microenvironment Predicts Survival in Pancreatic Ductal Adenocarcinoma: Heterogeneity in Fibroblast Population
Authors: Hiromitsu Maehira, MD
Toru Miyake, MD, PhD
Hiroya Iida, MD, PhD
Aya Tokuda, MD
Haruki Mori, MD
Daiki Yasukawa, MD
Ken-ichi Mukaisho, MD, PhD
Tomoharu Shimizu, MD, PhD
Masaji Tani, MD, PhD
Publication date: 01-12-2019
Publisher: Springer International Publishing
Published in: Annals of Surgical Oncology / Issue 13/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-019-07891-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Vimentin Expression in Tumor Microenvironment Predicts Survival in Pancreatic Ductal Adenocarcinoma: Heterogeneity in Fibroblast Population

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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