A practical distribution pattern of α-SMA-positive carcinoma associated fibroblasts indicates poor prognosis of patients with pancreatic ductal adenocarcinoma
Purpose The present study aimed to clarify the distribution pattern of carcinoma associated fibroblasts (CAFs) across pancreatic ductal adenocarcinoma (PDAC) and its prognostic prediction value.Methods Data of two cohorts were retrospectively collected from consecutive patients who underwent primary...
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Elsevier
2025-02-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325000130 |
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| author | Bo Li Meilong Shi Yang Wang Penghao Li Xiaoyi Yin Guoxiao Zhang Xiaochao Kang Huan Wang Suizhi Gao Kailian Zheng Xiaohan Shi Xiongfei Xu Yukun Zhou Hui Jiang Wei Jing Shiwei Guo Gang Jin |
| author_facet | Bo Li Meilong Shi Yang Wang Penghao Li Xiaoyi Yin Guoxiao Zhang Xiaochao Kang Huan Wang Suizhi Gao Kailian Zheng Xiaohan Shi Xiongfei Xu Yukun Zhou Hui Jiang Wei Jing Shiwei Guo Gang Jin |
| author_sort | Bo Li |
| collection | DOAJ |
| description | Purpose The present study aimed to clarify the distribution pattern of carcinoma associated fibroblasts (CAFs) across pancreatic ductal adenocarcinoma (PDAC) and its prognostic prediction value.Methods Data of two cohorts were retrospectively collected from consecutive patients who underwent primary pancreatic resection from January 2015 to December 2017. We used tumor specimens to screen out the most suitable markers for the spatial distribution analysis for CAFs subpopulations. We utilized a tissue microarray to assess the spatial intensity of α-SMA expression within the tumor microenvironment. Specifically, we classified CAFs into two types based on their α-SMA spatial expression. Type II CAFs were designated as those located in the juxtatumoural stroma with α-SMA expression that was moderate or higher, and those in the peripheral stroma with α-SMA expression that was less than moderate. All other cases, where the α-SMA expression did not meet these criteria, were categorized as Type I CAFs. Multivariable Cox proportional hazards regression was used to assess risk factors associated with patient outcomes. RNA sequencing data were obtained from bulk tumor samples and isolated CAFs from patients to reveal the distinct pattern and elucidated their fundamental characteristics.Results The α-SMA spatial intensity was the most suitable variable for representative of CAFs spatial characteristics. Patients with Type Ⅰ CAFs were more likely to be allocated into N1 or N2 of the N stage and Ⅱ and Ⅲ of the TNM stage. The spatial distribution pattern of CAFs (Type Ⅰ v.s. Type Ⅱ: HR, 1.568; 95 % CI, 1.053–2.334; P = 0.027) was an independent prognostic factor in the discovery cohort, so as in the validation (Type Ⅰ vs. Type Ⅱ: HR, 2.197; 95 % CI, 1.410–3.422; P = 0.001). RNA sequencing analysis revealed that the differentially expressed genes (DEGs) in Type I CAFs are closely associated with those in corresponding tumor tissues, highlighting the enhanced biological significance of immune-related and oncogenic invasive pathways.Conclusions Our findings that two types of α-SMA-positive CAFs with different spatial patterns present heterogeneously across tissues of PDACs and correlated with patients’ outcomes. The spatial location of CAFs may facilitate patients’ selection in precision medicine of PDACs. |
| format | Article |
| id | doaj-art-4060082c2c3b4b1d8e0c0e4957a9abc1 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-4060082c2c3b4b1d8e0c0e4957a9abc12025-01-22T05:41:37ZengElsevierTranslational Oncology1936-52332025-02-0152102282A practical distribution pattern of α-SMA-positive carcinoma associated fibroblasts indicates poor prognosis of patients with pancreatic ductal adenocarcinomaBo Li0Meilong Shi1Yang Wang2Penghao Li3Xiaoyi Yin4Guoxiao Zhang5Xiaochao Kang6Huan Wang7Suizhi Gao8Kailian Zheng9Xiaohan Shi10Xiongfei Xu11Yukun Zhou12Hui Jiang13Wei Jing14Shiwei Guo15Gang Jin16Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, China; Department of Hepatobiliary Pancreatic Surgery, Naval Medical Center, Naval Medical University (Second Military Medical University), 338 West Huaihai Road, Shanghai, 200052, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, ChinaDepartment of Pathology, Shanghai Fourth People's Hospital, Tongji University School of Medicine, 1279 Sanmen Road, Shanghai 200434, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Naval Medical Center, Naval Medical University (Second Military Medical University), 338 West Huaihai Road, Shanghai, 200052, ChinaDepartment of Pathology, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, China; Corresponding authors at: Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, China.Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, China; Corresponding authors at: Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, China.Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, China; Corresponding authors at: Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200433, China.Purpose The present study aimed to clarify the distribution pattern of carcinoma associated fibroblasts (CAFs) across pancreatic ductal adenocarcinoma (PDAC) and its prognostic prediction value.Methods Data of two cohorts were retrospectively collected from consecutive patients who underwent primary pancreatic resection from January 2015 to December 2017. We used tumor specimens to screen out the most suitable markers for the spatial distribution analysis for CAFs subpopulations. We utilized a tissue microarray to assess the spatial intensity of α-SMA expression within the tumor microenvironment. Specifically, we classified CAFs into two types based on their α-SMA spatial expression. Type II CAFs were designated as those located in the juxtatumoural stroma with α-SMA expression that was moderate or higher, and those in the peripheral stroma with α-SMA expression that was less than moderate. All other cases, where the α-SMA expression did not meet these criteria, were categorized as Type I CAFs. Multivariable Cox proportional hazards regression was used to assess risk factors associated with patient outcomes. RNA sequencing data were obtained from bulk tumor samples and isolated CAFs from patients to reveal the distinct pattern and elucidated their fundamental characteristics.Results The α-SMA spatial intensity was the most suitable variable for representative of CAFs spatial characteristics. Patients with Type Ⅰ CAFs were more likely to be allocated into N1 or N2 of the N stage and Ⅱ and Ⅲ of the TNM stage. The spatial distribution pattern of CAFs (Type Ⅰ v.s. Type Ⅱ: HR, 1.568; 95 % CI, 1.053–2.334; P = 0.027) was an independent prognostic factor in the discovery cohort, so as in the validation (Type Ⅰ vs. Type Ⅱ: HR, 2.197; 95 % CI, 1.410–3.422; P = 0.001). RNA sequencing analysis revealed that the differentially expressed genes (DEGs) in Type I CAFs are closely associated with those in corresponding tumor tissues, highlighting the enhanced biological significance of immune-related and oncogenic invasive pathways.Conclusions Our findings that two types of α-SMA-positive CAFs with different spatial patterns present heterogeneously across tissues of PDACs and correlated with patients’ outcomes. The spatial location of CAFs may facilitate patients’ selection in precision medicine of PDACs.http://www.sciencedirect.com/science/article/pii/S1936523325000130Pancreatic ductal adenocarcinomaSpatial distribution patternCarcinoma associated fibroblastImmunohistochemistryPatient selection |
| spellingShingle | Bo Li Meilong Shi Yang Wang Penghao Li Xiaoyi Yin Guoxiao Zhang Xiaochao Kang Huan Wang Suizhi Gao Kailian Zheng Xiaohan Shi Xiongfei Xu Yukun Zhou Hui Jiang Wei Jing Shiwei Guo Gang Jin A practical distribution pattern of α-SMA-positive carcinoma associated fibroblasts indicates poor prognosis of patients with pancreatic ductal adenocarcinoma Translational Oncology Pancreatic ductal adenocarcinoma Spatial distribution pattern Carcinoma associated fibroblast Immunohistochemistry Patient selection |
| title | A practical distribution pattern of α-SMA-positive carcinoma associated fibroblasts indicates poor prognosis of patients with pancreatic ductal adenocarcinoma |
| title_full | A practical distribution pattern of α-SMA-positive carcinoma associated fibroblasts indicates poor prognosis of patients with pancreatic ductal adenocarcinoma |
| title_fullStr | A practical distribution pattern of α-SMA-positive carcinoma associated fibroblasts indicates poor prognosis of patients with pancreatic ductal adenocarcinoma |
| title_full_unstemmed | A practical distribution pattern of α-SMA-positive carcinoma associated fibroblasts indicates poor prognosis of patients with pancreatic ductal adenocarcinoma |
| title_short | A practical distribution pattern of α-SMA-positive carcinoma associated fibroblasts indicates poor prognosis of patients with pancreatic ductal adenocarcinoma |
| title_sort | practical distribution pattern of α sma positive carcinoma associated fibroblasts indicates poor prognosis of patients with pancreatic ductal adenocarcinoma |
| topic | Pancreatic ductal adenocarcinoma Spatial distribution pattern Carcinoma associated fibroblast Immunohistochemistry Patient selection |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325000130 |
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