Blood small extracellular vesicles derived miRNAs to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis
Abstract Background The differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) is clinically challenging due to a lack of minimally invasive diagnosis methods. MicroRNAs (miRNAs) derived from small extracellular vesicles (EVs) in the blood have been reported...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-09-01
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| Series: | Clinical and Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ctm2.520 |
| _version_ | 1819002517725380608 |
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| author | Shiwei Guo Hao Qin Ke Liu Huan Wang Sijia Bai Shiyi Liu Zhuo Shao Yanan Zhang Bin Song Xiaoya Xu Jing Shen Peng Zeng Xiaohan Shi Hao Chen Suizhi Gao Jiajia Xu Yaqi Pan Lei Xiong Fugen Li Dadong Zhang Xiaodong Jiao Gang Jin |
| author_facet | Shiwei Guo Hao Qin Ke Liu Huan Wang Sijia Bai Shiyi Liu Zhuo Shao Yanan Zhang Bin Song Xiaoya Xu Jing Shen Peng Zeng Xiaohan Shi Hao Chen Suizhi Gao Jiajia Xu Yaqi Pan Lei Xiong Fugen Li Dadong Zhang Xiaodong Jiao Gang Jin |
| author_sort | Shiwei Guo |
| collection | DOAJ |
| description | Abstract Background The differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) is clinically challenging due to a lack of minimally invasive diagnosis methods. MicroRNAs (miRNAs) derived from small extracellular vesicles (EVs) in the blood have been reported as a promising diagnosis biomarker for various types of cancer. However, blood small EV miRNA signatures and their diagnostic value to differentiate between PDAC and CP remain to be determined. Methods In this study, 107 patients with PDAC or CP were recruited, and 90 patients were finally enrolled for a training cohort (n = 48) and test cohort (n = 42). Small RNA sequencing was used to assess the expression of blood small EV miRNAs in these patients. Results The linear model from the differentially expressed blood small EV miR‐95‐3p divided by miR‐26b‐5p showed an average sensitivity of 84.1% and an average specificity of 96.6% to identify PDAC from CP in the training cohort and the test cohort, respectively. When the model was combined with serum carbohydrate antigen 19‐9 (CA19‐9), the average sensitivity increased to 96.5%, and the average specificity remained at 96.4% of both cohorts, which demonstrated the best performance of all the published biomarkers for distinguishing between PDAC and CP. The causal analysis performed using the Bayesian network demonstrated that miR‐95‐3p was associated with a “consequence” of “cancer” and miR‐26b‐5p as a “cause” of “pancreatitis.” A subgroup analysis revealed that blood small EV miR‐335‐5p/miR‐340‐5p could predict metastases in both cohorts and was associated with an overall survival (p = 0.020). Conclusions This study indicated that blood small EV miR‐95‐3p/miR‐26b‐5p and its combination with serum levels of CA19‐9 could separate PDAC from CP, and miR‐335‐5p/miR‐340‐5p was identified to associate with PDAC metastasis and poor prognosis. These results suggested the potentiality of blood small EV miRNAs as differential diagnosis and metastases biomarkers of PDAC. |
| first_indexed | 2024-12-20T23:06:22Z |
| format | Article |
| id | doaj.art-13dcfc88aeee417aa47ae3e34fe7eeb4 |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-12-20T23:06:22Z |
| publishDate | 2021-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj.art-13dcfc88aeee417aa47ae3e34fe7eeb42022-12-21T19:23:51ZengWileyClinical and Translational Medicine2001-13262021-09-01119n/an/a10.1002/ctm2.520Blood small extracellular vesicles derived miRNAs to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitisShiwei Guo0Hao Qin1Ke Liu2Huan Wang3Sijia Bai4Shiyi Liu5Zhuo Shao6Yanan Zhang7Bin Song8Xiaoya Xu9Jing Shen10Peng Zeng11Xiaohan Shi12Hao Chen13Suizhi Gao14Jiajia Xu15Yaqi Pan16Lei Xiong17Fugen Li18Dadong Zhang19Xiaodong Jiao20Gang Jin21Department of Hepatobiliary Pancreatic Surgery Changhai Hospital Naval Medical University Shanghai China3D Medicines Inc. Shanghai ChinaDepartment of Medical Oncology Changzheng Hospital Naval Medical University Shanghai ChinaDepartment of Hepatobiliary Pancreatic Surgery Changhai Hospital Naval Medical University Shanghai ChinaDepartment of Hepatobiliary Pancreatic Surgery Changhai Hospital Naval Medical University Shanghai China3D Medicines Inc. Shanghai ChinaDepartment of Hepatobiliary Pancreatic Surgery Changhai Hospital Naval Medical University Shanghai China3D Medicines Inc. Shanghai ChinaDepartment of Hepatobiliary Pancreatic Surgery Changhai Hospital Naval Medical University Shanghai China3D Medicines Inc. Shanghai ChinaDepartment of Hepatobiliary Pancreatic Surgery Changhai Hospital Naval Medical University Shanghai China3D Medicines Inc. Shanghai ChinaDepartment of Hepatobiliary Pancreatic Surgery Changhai Hospital Naval Medical University Shanghai China3D Medicines Inc. Shanghai ChinaDepartment of Hepatobiliary Pancreatic Surgery Changhai Hospital Naval Medical University Shanghai China3D Medicines Inc. Shanghai ChinaDepartment of Hepatobiliary Pancreatic Surgery Changhai Hospital Naval Medical University Shanghai China3D Medicines Inc. Shanghai China3D Medicines Inc. Shanghai China3D Medicines Inc. Shanghai ChinaDepartment of Medical Oncology Changzheng Hospital Naval Medical University Shanghai ChinaDepartment of Hepatobiliary Pancreatic Surgery Changhai Hospital Naval Medical University Shanghai ChinaAbstract Background The differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) is clinically challenging due to a lack of minimally invasive diagnosis methods. MicroRNAs (miRNAs) derived from small extracellular vesicles (EVs) in the blood have been reported as a promising diagnosis biomarker for various types of cancer. However, blood small EV miRNA signatures and their diagnostic value to differentiate between PDAC and CP remain to be determined. Methods In this study, 107 patients with PDAC or CP were recruited, and 90 patients were finally enrolled for a training cohort (n = 48) and test cohort (n = 42). Small RNA sequencing was used to assess the expression of blood small EV miRNAs in these patients. Results The linear model from the differentially expressed blood small EV miR‐95‐3p divided by miR‐26b‐5p showed an average sensitivity of 84.1% and an average specificity of 96.6% to identify PDAC from CP in the training cohort and the test cohort, respectively. When the model was combined with serum carbohydrate antigen 19‐9 (CA19‐9), the average sensitivity increased to 96.5%, and the average specificity remained at 96.4% of both cohorts, which demonstrated the best performance of all the published biomarkers for distinguishing between PDAC and CP. The causal analysis performed using the Bayesian network demonstrated that miR‐95‐3p was associated with a “consequence” of “cancer” and miR‐26b‐5p as a “cause” of “pancreatitis.” A subgroup analysis revealed that blood small EV miR‐335‐5p/miR‐340‐5p could predict metastases in both cohorts and was associated with an overall survival (p = 0.020). Conclusions This study indicated that blood small EV miR‐95‐3p/miR‐26b‐5p and its combination with serum levels of CA19‐9 could separate PDAC from CP, and miR‐335‐5p/miR‐340‐5p was identified to associate with PDAC metastasis and poor prognosis. These results suggested the potentiality of blood small EV miRNAs as differential diagnosis and metastases biomarkers of PDAC.https://doi.org/10.1002/ctm2.520chronic pancreatitisdifferential diagnosispancreatic ductal adenocarcinomasmall extracellular vesicles miRNAs |
| spellingShingle | Shiwei Guo Hao Qin Ke Liu Huan Wang Sijia Bai Shiyi Liu Zhuo Shao Yanan Zhang Bin Song Xiaoya Xu Jing Shen Peng Zeng Xiaohan Shi Hao Chen Suizhi Gao Jiajia Xu Yaqi Pan Lei Xiong Fugen Li Dadong Zhang Xiaodong Jiao Gang Jin Blood small extracellular vesicles derived miRNAs to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis Clinical and Translational Medicine chronic pancreatitis differential diagnosis pancreatic ductal adenocarcinoma small extracellular vesicles miRNAs |
| title | Blood small extracellular vesicles derived miRNAs to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis |
| title_full | Blood small extracellular vesicles derived miRNAs to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis |
| title_fullStr | Blood small extracellular vesicles derived miRNAs to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis |
| title_full_unstemmed | Blood small extracellular vesicles derived miRNAs to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis |
| title_short | Blood small extracellular vesicles derived miRNAs to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis |
| title_sort | blood small extracellular vesicles derived mirnas to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis |
| topic | chronic pancreatitis differential diagnosis pancreatic ductal adenocarcinoma small extracellular vesicles miRNAs |
| url | https://doi.org/10.1002/ctm2.520 |
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