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...
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Wiley
2021
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oai:doaj.org-article:13dcfc88aeee417aa47ae3e34fe7eeb42021-11-11T12:06:39ZBlood small extracellular vesicles derived miRNAs to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis2001-132610.1002/ctm2.520https://doaj.org/article/13dcfc88aeee417aa47ae3e34fe7eeb42021-09-01T00:00:00Zhttps://doi.org/10.1002/ctm2.520https://doaj.org/toc/2001-1326Abstract 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.Shiwei GuoHao QinKe LiuHuan WangSijia BaiShiyi LiuZhuo ShaoYanan ZhangBin SongXiaoya XuJing ShenPeng ZengXiaohan ShiHao ChenSuizhi GaoJiajia XuYaqi PanLei XiongFugen LiDadong ZhangXiaodong JiaoGang JinWileyarticlechronic pancreatitisdifferential diagnosispancreatic ductal adenocarcinomasmall extracellular vesicles miRNAsMedicine (General)R5-920ENClinical and Translational Medicine, Vol 11, Iss 9, Pp n/a-n/a (2021) |
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| collection |
DOAJ |
| language |
EN |
| topic |
chronic pancreatitis differential diagnosis pancreatic ductal adenocarcinoma small extracellular vesicles miRNAs Medicine (General) R5-920 |
| spellingShingle |
chronic pancreatitis differential diagnosis pancreatic ductal adenocarcinoma small extracellular vesicles miRNAs Medicine (General) R5-920 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
blood small extracellular vesicles derived mirnas to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis |
| publisher |
Wiley |
| publishDate |
2021 |
| url |
https://doaj.org/article/13dcfc88aeee417aa47ae3e34fe7eeb4 |
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