Diagnostic value of exosome miRNA-21 in bile for cholangiocarcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Xiaoqian ¹ , RAN Fengying ² , WU Lun ¹ , YUAN Fangjun ¹ , CHEN Qinhua ² ,  HU Hongsheng ¹

1. Department of Hepatopancreatobiliary Surgery, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan,Hubei 442008, P. R. China;
2. Clinical Laboratory, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P. R. China;

Corresponding author：

HU Hongsheng, Email: huhongsheng2000@163.com

Keywords：

cholangiocarcinoma; bile exosome; microRNA-21; diagnosis biomarker

DOI：

10.7507/1007-9424.202208061

Video：

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Objective To investigate the expression level of exosome microRNA-21 (miRNA-21) in the bile and its clinical diagnostic value for the patients with cholangiocarcinoma. Methods In this study, 45 cases of cholangiocarcinoma admitted to Dongfeng General Hospital from August 2019 to December 2021 and met the inclusion criteria were selected and 35 patients with benign diseases of bile duct (choledocholithiasis or benign stricture of bile duct) during the same period were selected as control. The exosome in the bile was extracted by hypervelocity centrifugation method and identified. The exosome miRNA was extracted from the bile using a kit, then the expression level of miRNA-21 was detected by real-time fluorescent quantitative PCR. The diagnostic value of exosome miRNA-21 in the bile for cholangiocarcinoma was analyzed by receiver operating characteristic curve (ROC). Results The isolated exosome in the bile conformed to the characteristics of recognized exosome and the concentration was higher. The average expression level of exosome miRNA-21 in the bile of the patients with cholangiocarcinoma was statistically higher than that in the patients with benign diseases of bile duct (59.45 verses 25.41, t=3.445, P<0.001). The area under the ROC curve was 0.715 [95%CI (0.602, 0.827), P=0.001]. The sensitivity and specificity of miRNA-21 in the diagnosis of cholangiocarcinoma were 75.6% and 62.9%, respectively. Conclusion From the results of this study, exosome miRNA-21 expression in bile is higher and it may be a potential early diagnostic marker for patients with cholangiocarcinoma.

Citation： LIU Xiaoqian, RAN Fengying, WU Lun, YUAN Fangjun, CHEN Qinhua, HU Hongsheng. Diagnostic value of exosome miRNA-21 in bile for cholangiocarcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(1): 48-52. doi: 10.7507/1007-9424.202208061 Copy

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2.	央茂, 李永盛, 吴文广, 等. 液态活检技术在胆道肿瘤诊治中的应用进展. 中华肝胆外科杂志, 2021, 27(6): 472-476.
3.	Liu XQ, Tufman A, Kiefl R, et al. Identification of lung adenocarcinoma-specific exosome RNAs in peripheral blood by RNA-Seq analysis. Eur Rev Med Pharmacol Sci, 2020, 24(4): 1877-1886.
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5.	李永盛, 王许安, 吴文广, 等. 外泌体在胆道恶性肿瘤诊治中应用进展. 中国实用外科杂志, 2021, 41(10): 1178-1180, 1185.
6.	刘艳, 戴鹏, 朱运峰. 外泌体作为肿瘤标志物的研究进展. 中国生物工程杂志, 2019, 39(8): 74-79.
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10.	Nakaoka T, Saito Y, Saito H. Aberrant DNA methylation as a biomarker and a therapeutic target of cholangiocarcinoma. Int J Mol Sci, 2017, 18(6): 1111. doi: 10.3390/ijms18061111.
11.	Correa-Gallego C, Maddalo D, Doussot A, et al. Circulating plasma levels of microRNA-21 and microRNA-221 are potential diagnostic markers for primary intrahepatic cholangiocarcinoma. PLoS One, 2016, 11(9): e0163699. doi: 10.1371/journal.pone.0163699.
12.	Kishimoto T, Eguchi H, Nagano H, et al. Plasma miR-21 is a novel diagnostic biomarker for biliary tract cancer. Cancer Sci, 2013, 104(12): 1626-1631.
13.	Liang H, Gong F, Zhang S, et al. The origin, function, and diagnostic potential of extracellular microRNAs in human body fluids. Wiley Interdiscip Rev RNA, 2014, 5(2): 285-300.
14.	Dang XT, Zeng XR. Targeted therapeutic delivery using engineered exosomes and its applications in cardiovascular diseases. Gene, 2016, 575(2 Pt 2): 377-384.
15.	Samandari M, Julia MG, Rice A, et al. Liquid biopsies for management of pancreatic cancer. Transl Res, 2018, 201: 98-127.
16.	Li X, Wang Y, Wang Q, et al. Exosomes in cancer: small transporters with big functions. Cancer Lett, 2018, 435: 55-65.
17.	Wang M, Yu F, Ding H, et al. Emerging function and clinical values of exosomal microRNAs in cancer. Mol Ther Nucleic Acids, 2019, 16: 791-804.
18.	Joyce DP, Kerin MJ, Dwyer RM. Exosome-encapsulated microRNAs as circulating biomarkers for breast cancer. Int J Cancer, 2016, 139(7): 1443-1448.
19.	Garcia-Romero N, Esteban-Rubio S, Rackov G, et al. Extracellular vesicles compartment in liquid biopsies: Clinical application. Mol Aspects Med, 2018, 60: 27-37.
20.	Severino V, Dumonceau JM, Delhaye M, et al. Extracellular vesicles in bile as markers of malignant biliary stenoses. Gastroenterology, 2017, 153(2): 495-504.
21.	Li L, Masica D, Ishida M, et al. Human bile contains microRNA-laden extracellular vesicles that can be used for cholangio-carcinoma diagnosis. Hepatology, 2014, 60(3): 896-907.
22.	Li P, Kaslan M, Lee SH, et al. Progress in exosome isolation techniques. Theranostics, 2017, 7(3): 789-804.

1. Kim J, Tan Z, Lubman DM. Exosome enrichment of human serum using multiple cycles of centrifugation. Electrophoresis, 2015, 36(17): 2017-2026.
2. 央茂, 李永盛, 吴文广, 等. 液态活检技术在胆道肿瘤诊治中的应用进展. 中华肝胆外科杂志, 2021, 27(6): 472-476.
3. Liu XQ, Tufman A, Kiefl R, et al. Identification of lung adenocarcinoma-specific exosome RNAs in peripheral blood by RNA-Seq analysis. Eur Rev Med Pharmacol Sci, 2020, 24(4): 1877-1886.
4. 闵贝贝, 朱莉, 曾娟. 结直肠癌患者血浆外泌体中miRNA-23b的表达及其临床意义. 实用医学杂志, 2020, 36(7): 863-868.
5. 李永盛, 王许安, 吴文广, 等. 外泌体在胆道恶性肿瘤诊治中应用进展. 中国实用外科杂志, 2021, 41(10): 1178-1180, 1185.
6. 刘艳, 戴鹏, 朱运峰. 外泌体作为肿瘤标志物的研究进展. 中国生物工程杂志, 2019, 39(8): 74-79.
7. Macfarlane CL, Quek S, Pionnier N, et al. The insufficiency of circulating miRNA and DNA as diagnostic tools or as biomarkers of treatment efficacy for Onchocerca volvulus. Sci Rep, 2020, 10(1): 6672. doi: 10.1038/s41598-020-63249-4.
8. Weber JA, Baxter DH, Zhang S, et al. The microRNA spectrum in 12 body fluids. Clin Chem, 2010, 56(11): 1733-1741.
9. Arbelaiz A, Azkargorta M, Krawczyk M, et al. Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma. Hepatology, 2017, 66(4): 1125-1143.
10. Nakaoka T, Saito Y, Saito H. Aberrant DNA methylation as a biomarker and a therapeutic target of cholangiocarcinoma. Int J Mol Sci, 2017, 18(6): 1111. doi: 10.3390/ijms18061111.
11. Correa-Gallego C, Maddalo D, Doussot A, et al. Circulating plasma levels of microRNA-21 and microRNA-221 are potential diagnostic markers for primary intrahepatic cholangiocarcinoma. PLoS One, 2016, 11(9): e0163699. doi: 10.1371/journal.pone.0163699.
12. Kishimoto T, Eguchi H, Nagano H, et al. Plasma miR-21 is a novel diagnostic biomarker for biliary tract cancer. Cancer Sci, 2013, 104(12): 1626-1631.
13. Liang H, Gong F, Zhang S, et al. The origin, function, and diagnostic potential of extracellular microRNAs in human body fluids. Wiley Interdiscip Rev RNA, 2014, 5(2): 285-300.
14. Dang XT, Zeng XR. Targeted therapeutic delivery using engineered exosomes and its applications in cardiovascular diseases. Gene, 2016, 575(2 Pt 2): 377-384.
15. Samandari M, Julia MG, Rice A, et al. Liquid biopsies for management of pancreatic cancer. Transl Res, 2018, 201: 98-127.
16. Li X, Wang Y, Wang Q, et al. Exosomes in cancer: small transporters with big functions. Cancer Lett, 2018, 435: 55-65.
17. Wang M, Yu F, Ding H, et al. Emerging function and clinical values of exosomal microRNAs in cancer. Mol Ther Nucleic Acids, 2019, 16: 791-804.
18. Joyce DP, Kerin MJ, Dwyer RM. Exosome-encapsulated microRNAs as circulating biomarkers for breast cancer. Int J Cancer, 2016, 139(7): 1443-1448.
19. Garcia-Romero N, Esteban-Rubio S, Rackov G, et al. Extracellular vesicles compartment in liquid biopsies: Clinical application. Mol Aspects Med, 2018, 60: 27-37.
20. Severino V, Dumonceau JM, Delhaye M, et al. Extracellular vesicles in bile as markers of malignant biliary stenoses. Gastroenterology, 2017, 153(2): 495-504.
21. Li L, Masica D, Ishida M, et al. Human bile contains microRNA-laden extracellular vesicles that can be used for cholangio-carcinoma diagnosis. Hepatology, 2014, 60(3): 896-907.
22. Li P, Kaslan M, Lee SH, et al. Progress in exosome isolation techniques. Theranostics, 2017, 7(3): 789-804.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Diagnostic value of exosome miRNA-21 in bile for cholangiocarcinoma

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