Spatial profiling of endoplasmic reticulum stress markers in tumor associated cells predicts patient outcomes in pancreatic cancer
Introduction: The impact of endoplasmic reticulum (ER) stress in tumor-associated cells, such as cancer associated fibroblasts (CAFs), immune cells and endothelial cells, on patient outcomes in clinical specimens have not been examined. For the first time, we characterized the expression and spatial...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558624001568 |
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| author | Georgia Porter Murray D. Norris Minoti Apte Angelica M. Merlot |
| author_facet | Georgia Porter Murray D. Norris Minoti Apte Angelica M. Merlot |
| author_sort | Georgia Porter |
| collection | DOAJ |
| description | Introduction: The impact of endoplasmic reticulum (ER) stress in tumor-associated cells, such as cancer associated fibroblasts (CAFs), immune cells and endothelial cells, on patient outcomes in clinical specimens have not been examined. For the first time, we characterized the expression and spatial locations of ER stress markers, BiP and CHOP, in tumor-associated cells and assessed their prognostic significance in a panel of pancreatic ductal adenocarcinoma (PDAC) patient samples. Methods: Multiplex immunofluorescence was performed on tumor microarrays and images were analyzed using HALO AI software. Results: BiP and CHOP were upregulated in CAFs and endothelial cells in PDAC sections relative to non-neoplastic pancreas sections. High BiP expression in CAFs and endothelial cells was associated with greater vascular invasion and in immune cells was correlated with increased tumor size. High CHOP expression in immune cells correlated with poor patient survival. CAFs and immune cells were more likely to express BiP or CHOP when located close (< 20 μm) to tumor cells. High expression of CHOP in CAFs close to tumor cells correlated with improved patient survival. Conclusion: For the first time, this study demonstrated that ER stress occurs in CAFs and immune cells predominantly in proximity to tumor cells in PDAC patient tissue. The correlation of high ER stress in immune cells with poor patient survival highlights the importance of the TME and the use of spatial analysis for the identification of novel biomarkers. |
| format | Article |
| id | doaj-art-bec419942cea4fdba10c8de894c3e202 |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-bec419942cea4fdba10c8de894c3e2022025-02-03T04:16:35ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-02-0160101115Spatial profiling of endoplasmic reticulum stress markers in tumor associated cells predicts patient outcomes in pancreatic cancerGeorgia Porter0Murray D. Norris1Minoti Apte2Angelica M. Merlot3Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2031, Australia; School of Clinical Medicine, Faculty of Medicine & Health, University of New South Wales, Kensington, New South Wales 2031, Australia; UNSW Centre for Childhood Cancer Research, Faculty of Medicine &Health, University of New South Wales, Kensington, New South Wales 2031, AustraliaChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2031, Australia; School of Clinical Medicine, Faculty of Medicine & Health, University of New South Wales, Kensington, New South Wales 2031, Australia; UNSW Centre for Childhood Cancer Research, Faculty of Medicine &Health, University of New South Wales, Kensington, New South Wales 2031, AustraliaPancreatic Research Group, South Western Sydney Clinical Campuses, Faculty of Medicine and Health, UNSW Sydney, NSW 2052, Australia; Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, AustraliaChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2031, Australia; School of Clinical Medicine, Faculty of Medicine & Health, University of New South Wales, Kensington, New South Wales 2031, Australia; UNSW Centre for Childhood Cancer Research, Faculty of Medicine &Health, University of New South Wales, Kensington, New South Wales 2031, Australia; Australian Centre for NanoMedicine, University of New South Wales, Sydney, NSW 2031, Australia; Corresponding author at: Lowy Cancer Research Centre, C25/9 High St, Kensington, The University of New South Wales, New South Wales 2031, Australia.Introduction: The impact of endoplasmic reticulum (ER) stress in tumor-associated cells, such as cancer associated fibroblasts (CAFs), immune cells and endothelial cells, on patient outcomes in clinical specimens have not been examined. For the first time, we characterized the expression and spatial locations of ER stress markers, BiP and CHOP, in tumor-associated cells and assessed their prognostic significance in a panel of pancreatic ductal adenocarcinoma (PDAC) patient samples. Methods: Multiplex immunofluorescence was performed on tumor microarrays and images were analyzed using HALO AI software. Results: BiP and CHOP were upregulated in CAFs and endothelial cells in PDAC sections relative to non-neoplastic pancreas sections. High BiP expression in CAFs and endothelial cells was associated with greater vascular invasion and in immune cells was correlated with increased tumor size. High CHOP expression in immune cells correlated with poor patient survival. CAFs and immune cells were more likely to express BiP or CHOP when located close (< 20 μm) to tumor cells. High expression of CHOP in CAFs close to tumor cells correlated with improved patient survival. Conclusion: For the first time, this study demonstrated that ER stress occurs in CAFs and immune cells predominantly in proximity to tumor cells in PDAC patient tissue. The correlation of high ER stress in immune cells with poor patient survival highlights the importance of the TME and the use of spatial analysis for the identification of novel biomarkers.http://www.sciencedirect.com/science/article/pii/S1476558624001568Pancreatic cancerTumour microenvironmentCancer associated fibroblastsEndoplasmic reticulum stress |
| spellingShingle | Georgia Porter Murray D. Norris Minoti Apte Angelica M. Merlot Spatial profiling of endoplasmic reticulum stress markers in tumor associated cells predicts patient outcomes in pancreatic cancer Neoplasia: An International Journal for Oncology Research Pancreatic cancer Tumour microenvironment Cancer associated fibroblasts Endoplasmic reticulum stress |
| title | Spatial profiling of endoplasmic reticulum stress markers in tumor associated cells predicts patient outcomes in pancreatic cancer |
| title_full | Spatial profiling of endoplasmic reticulum stress markers in tumor associated cells predicts patient outcomes in pancreatic cancer |
| title_fullStr | Spatial profiling of endoplasmic reticulum stress markers in tumor associated cells predicts patient outcomes in pancreatic cancer |
| title_full_unstemmed | Spatial profiling of endoplasmic reticulum stress markers in tumor associated cells predicts patient outcomes in pancreatic cancer |
| title_short | Spatial profiling of endoplasmic reticulum stress markers in tumor associated cells predicts patient outcomes in pancreatic cancer |
| title_sort | spatial profiling of endoplasmic reticulum stress markers in tumor associated cells predicts patient outcomes in pancreatic cancer |
| topic | Pancreatic cancer Tumour microenvironment Cancer associated fibroblasts Endoplasmic reticulum stress |
| url | http://www.sciencedirect.com/science/article/pii/S1476558624001568 |
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