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.
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 PDACpatients 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 PDACpatients. 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.
Authors: Marika Musielak; Oliwia Piwocka; Katarzyna Kulcenty; Karolina Ampuła; Beata Adamczyk; Igor Piotrowski; Magdalena Fundowicz; Marta Kruszyna-Mochalska; Wiktoria M Suchorska; Julian Malicki Journal: Am J Cancer Res Date: 2022-09-15 Impact factor: 5.942
Authors: Damián Sánchez-Ramírez; Rafael Medrano-Guzmán; Fernando Candanedo-González; Jazmín De Anda-González; Luis Enrique García-Rios; Vadim Pérez-Koldenkova; Marcos Gutiérrez-de la Barrera; Sara Rodríguez-Enríquez; Marco Velasco-Velázquez; Silvia Cecilia Pacheco-Velázquez; Patricia Piña-Sánchez; Héctor Mayani; Alejandro Gómez-Delgado; Alberto Monroy-García; Ana Karen Martínez-Lara; Juan José Montesinos Journal: Eur J Histochem Date: 2022-02-17 Impact factor: 3.188