Vimentin Expression in Tumor Microenvironment Predicts Survival in Pancreatic Ductal Adenocarcinoma: Heterogeneity in Fibroblast Population
| Autor: | Tomoharu Shimizu, Hiroya Iida, Daiki Yasukawa, Aya Tokuda, Hiromitsu Maehira, Masaji Tani, Haruki Mori, Toru Miyake, Ken-ichi Mukaisho |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Population Vimentin Adenocarcinoma 03 medical and health sciences 0302 clinical medicine Cancer-Associated Fibroblasts Surgical oncology medicine Biomarkers Tumor Tumor Microenvironment Humans education Fibroblast Aged Cell Proliferation Retrospective Studies education.field_of_study Tumor microenvironment biology business.industry Cancer Middle Aged medicine.disease Prognosis Primary tumor Pancreatic Neoplasms Survival Rate medicine.anatomical_structure Oncology Chemotherapy Adjuvant 030220 oncology & carcinogenesis biology.protein Cancer research Immunohistochemistry 030211 gastroenterology & hepatology Surgery Female business Carcinoma Pancreatic Ductal Follow-Up Studies |
| Zdroj: | Annals of surgical oncology. 26(13) |
| ISSN: | 1534-4681 |
| Popis: | 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, 33.3months for low co-expression vs. 18.2months 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. |
| Databáze: | OpenAIRE |
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