Skip to main content
Top
Published in: BMC Gastroenterology 1/2020

Open Access 01-12-2020 | Chronic Pancreatitis | Research article

Exosomal miRNA signatures of pancreatic lesions

Authors: Caterina Vicentini, Federica Calore, Giovanni Nigita, Paolo Fadda, Michele Simbolo, Nicola Sperandio, Claudio Luchini, Rita T. Lawlor, Carlo Maria Croce, Vincenzo Corbo, Matteo Fassan, Aldo Scarpa

Published in: BMC Gastroenterology | Issue 1/2020

Login to get access

Abstract

Background

Pancreatic and peri-pancreatic neoplasms encompass a variety of histotypes characterized by a heterogeneous prognostic impact. miRNAs are considered efficient candidate biomarkers due to their high stability in tissues and body fluids. We applied Nanostring profiling of circulating exosomal miRNAs to distinct pancreatic lesions in order to establish a source for biomarker development.

Methods

A series of 140 plasma samples obtained from patients affected by pancreatic ductal adenocarcinoma (PDAC, n = 58), pancreatic neuroendocrine tumors (PanNET, n = 42), intraductal papillary mucinous neoplasms (IPMN, n = 20), and ampulla of Vater carcinomas (AVC, n = 20) were analyzed. Comprehensive miRNA profiling was performed on plasma-derived exosomes. Relevant miRNAs were validated by qRT-PCR and in situ hybridization (ISH).

Results

Lesion specific miRNAs were identified through multiple disease comparisons. Selected miRNAs were validated in the plasma by qRT-PCR and at tissue level by ISH. We leveraged the presence of clinical subtypes with each disease cohort to identify miRNAs that are differentially enriched in aggressive phenotypes.

Conclusions

This study shows that pancreatic lesions are characterized by specific exosomal-miRNA signatures. We also provide the basis for further explorations in order to better understand the relevance of these signatures in pancreatic neoplasms.
Appendix
Available only for authorised users
Literature
1.
go back to reference Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7.PubMed Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7.PubMed
2.
go back to reference Zhou B, Xu JW, Cheng YG, Gao JY, Hu SY, Wang L, et al. Early detection of pancreatic cancer: where are we now and where are we going? Int J Cancer. 2017;141(2):231.PubMedCrossRef Zhou B, Xu JW, Cheng YG, Gao JY, Hu SY, Wang L, et al. Early detection of pancreatic cancer: where are we now and where are we going? Int J Cancer. 2017;141(2):231.PubMedCrossRef
4.
5.
go back to reference Capelli P, Fassan M, Scarpa A. Pathology - grading and staging of GEP-NETs. Best Pract Res Clin Gastroenterol. 2012;26(6):705.PubMedCrossRef Capelli P, Fassan M, Scarpa A. Pathology - grading and staging of GEP-NETs. Best Pract Res Clin Gastroenterol. 2012;26(6):705.PubMedCrossRef
6.
go back to reference Cancer Genome Atlas Research Network. Electronic address aadhe, Cancer Genome Atlas Research N. Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Cell. 2017;32(2):185.CrossRef Cancer Genome Atlas Research Network. Electronic address aadhe, Cancer Genome Atlas Research N. Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Cell. 2017;32(2):185.CrossRef
7.
go back to reference Scarpa A, Chang DK, Nones K, Corbo V, Patch AM, Bailey P, et al. Whole-genome landscape of pancreatic neuroendocrine tumours. Nature. 2017;543(7643):65.PubMedCrossRef Scarpa A, Chang DK, Nones K, Corbo V, Patch AM, Bailey P, et al. Whole-genome landscape of pancreatic neuroendocrine tumours. Nature. 2017;543(7643):65.PubMedCrossRef
8.
go back to reference Becker AE, Hernandez YG, Frucht H, Lucas AL. Pancreatic ductal adenocarcinoma: risk factors, screening, and early detection. World J Gastroenterol. 2014;20(32):11182.PubMedPubMedCentralCrossRef Becker AE, Hernandez YG, Frucht H, Lucas AL. Pancreatic ductal adenocarcinoma: risk factors, screening, and early detection. World J Gastroenterol. 2014;20(32):11182.PubMedPubMedCentralCrossRef
9.
go back to reference Pham A, Forsmark C. Chronic pancreatitis: review and update of etiology, risk factors, and management. F1000Res. 2018;7. Pham A, Forsmark C. Chronic pancreatitis: review and update of etiology, risk factors, and management. F1000Res. 2018;7.
10.
go back to reference Sadr-Azodi O, Oskarsson V, Discacciati A, Videhult P, Askling J, Ekbom A. Pancreatic Cancer following acute pancreatitis: a population-based matched cohort study. Am J Gastroenterol. 2018;113(11):1711.PubMedCrossRef Sadr-Azodi O, Oskarsson V, Discacciati A, Videhult P, Askling J, Ekbom A. Pancreatic Cancer following acute pancreatitis: a population-based matched cohort study. Am J Gastroenterol. 2018;113(11):1711.PubMedCrossRef
11.
go back to reference Riva G, Pea A, Pilati C, Fiadone G, Lawlor RT, Scarpa A, et al. Histo-molecular oncogenesis of pancreatic cancer: from precancerous lesions to invasive ductal adenocarcinoma. World J Gastrointest Oncol. 2018;10(10):317.PubMedPubMedCentralCrossRef Riva G, Pea A, Pilati C, Fiadone G, Lawlor RT, Scarpa A, et al. Histo-molecular oncogenesis of pancreatic cancer: from precancerous lesions to invasive ductal adenocarcinoma. World J Gastrointest Oncol. 2018;10(10):317.PubMedPubMedCentralCrossRef
12.
go back to reference Amato E, Molin MD, Mafficini A, Yu J, Malleo G, Rusev B, et al. Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas. J Pathol. 2014;233(3):217.PubMedPubMedCentralCrossRef Amato E, Molin MD, Mafficini A, Yu J, Malleo G, Rusev B, et al. Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas. J Pathol. 2014;233(3):217.PubMedPubMedCentralCrossRef
13.
go back to reference Hosoda W, Chianchiano P, Griffin JF, Pittman ME, Brosens LA, Noe M, et al. Genetic analyses of isolated high-grade pancreatic intraepithelial neoplasia (HG-PanIN) reveal paucity of alterations in TP53 and SMAD4. J Pathol. 2017;242(1):16.PubMedPubMedCentralCrossRef Hosoda W, Chianchiano P, Griffin JF, Pittman ME, Brosens LA, Noe M, et al. Genetic analyses of isolated high-grade pancreatic intraepithelial neoplasia (HG-PanIN) reveal paucity of alterations in TP53 and SMAD4. J Pathol. 2017;242(1):16.PubMedPubMedCentralCrossRef
14.
go back to reference Felsenstein M, Noe M, Masica DL, Hosoda W, Chianchiano P, Fischer CG, et al. IPMNs with co-occurring invasive cancers: neighbours but not always relatives. Gut. 2018;67(9):1652.PubMedCrossRef Felsenstein M, Noe M, Masica DL, Hosoda W, Chianchiano P, Fischer CG, et al. IPMNs with co-occurring invasive cancers: neighbours but not always relatives. Gut. 2018;67(9):1652.PubMedCrossRef
15.
go back to reference Pea A, Riva G, Bernasconi R, Sereni E, Lawlor RT, Scarpa A, et al. Ampulla of Vater carcinoma: molecular landscape and clinical implications. World J Gastrointest Oncol. 2018;10(11):370.PubMedPubMedCentralCrossRef Pea A, Riva G, Bernasconi R, Sereni E, Lawlor RT, Scarpa A, et al. Ampulla of Vater carcinoma: molecular landscape and clinical implications. World J Gastrointest Oncol. 2018;10(11):370.PubMedPubMedCentralCrossRef
16.
go back to reference He J, Ahuja N, Makary MA, Cameron JL, Eckhauser FE, Choti MA, et al. 2564 resected periampullary adenocarcinomas at a single institution: trends over three decades. HPB (Oxford). 2014;16(1):83.CrossRef He J, Ahuja N, Makary MA, Cameron JL, Eckhauser FE, Choti MA, et al. 2564 resected periampullary adenocarcinomas at a single institution: trends over three decades. HPB (Oxford). 2014;16(1):83.CrossRef
17.
go back to reference Albores-Saavedra J, Schwartz AM, Batich K, Henson DE. Cancers of the ampulla of vater: demographics, morphology, and survival based on 5,625 cases from the SEER program. J Surg Oncol. 2009;100(7):598.PubMedCrossRef Albores-Saavedra J, Schwartz AM, Batich K, Henson DE. Cancers of the ampulla of vater: demographics, morphology, and survival based on 5,625 cases from the SEER program. J Surg Oncol. 2009;100(7):598.PubMedCrossRef
18.
go back to reference Mafficini A, Amato E, Cataldo I, Rusev BC, Bertoncello L, Corbo V, et al. Ampulla of Vater carcinoma: sequencing analysis identifies TP53 status as a novel independent prognostic factor and potentially actionable ERBB, PI3K, and WNT pathways gene mutations. Ann Surg. 2018;267(1):149.PubMedCrossRef Mafficini A, Amato E, Cataldo I, Rusev BC, Bertoncello L, Corbo V, et al. Ampulla of Vater carcinoma: sequencing analysis identifies TP53 status as a novel independent prognostic factor and potentially actionable ERBB, PI3K, and WNT pathways gene mutations. Ann Surg. 2018;267(1):149.PubMedCrossRef
19.
go back to reference Nikolaidis P, Hammond NA, Day K, Yaghmai V, Wood CG 3rd, Mosbach DS, et al. Imaging features of benign and malignant ampullary and periampullary lesions. Radiographics. 2014;34(3):624.PubMedCrossRef Nikolaidis P, Hammond NA, Day K, Yaghmai V, Wood CG 3rd, Mosbach DS, et al. Imaging features of benign and malignant ampullary and periampullary lesions. Radiographics. 2014;34(3):624.PubMedCrossRef
23.
go back to reference Xi Y, Nakajima G, Gavin E, Morris CG, Kudo K, Hayashi K, et al. Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA. 2007;13(10):1668.PubMedPubMedCentralCrossRef Xi Y, Nakajima G, Gavin E, Morris CG, Kudo K, Hayashi K, et al. Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA. 2007;13(10):1668.PubMedPubMedCentralCrossRef
24.
go back to reference Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105(30):10513.PubMedPubMedCentralCrossRef Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105(30):10513.PubMedPubMedCentralCrossRef
25.
go back to reference Turchinovich A, Tonevitsky AG, Burwinkel B. Extracellular miRNA: a collision of two paradigms. Trends Biochem Sci. 2016;41(10):883.PubMedCrossRef Turchinovich A, Tonevitsky AG, Burwinkel B. Extracellular miRNA: a collision of two paradigms. Trends Biochem Sci. 2016;41(10):883.PubMedCrossRef
27.
go back to reference Aucher A, Rudnicka D, Davis DM. MicroRNAs transfer from human macrophages to hepato-carcinoma cells and inhibit proliferation. J Immunol. 2013;191(12):6250.PubMedCrossRef Aucher A, Rudnicka D, Davis DM. MicroRNAs transfer from human macrophages to hepato-carcinoma cells and inhibit proliferation. J Immunol. 2013;191(12):6250.PubMedCrossRef
28.
go back to reference Zhang Y, Li M, Wang H, Fisher WE, Lin PH, Yao Q, et al. Profiling of 95 microRNAs in pancreatic cancer cell lines and surgical specimens by real-time PCR analysis. World J Surg. 2009;33(4):698.PubMedPubMedCentralCrossRef Zhang Y, Li M, Wang H, Fisher WE, Lin PH, Yao Q, et al. Profiling of 95 microRNAs in pancreatic cancer cell lines and surgical specimens by real-time PCR analysis. World J Surg. 2009;33(4):698.PubMedPubMedCentralCrossRef
29.
go back to reference Yu J, Li A, Hong SM, Hruban RH, Goggins M. MicroRNA alterations of pancreatic intraepithelial neoplasias. Clin Cancer Res. 2012;18(4):981.PubMedCrossRef Yu J, Li A, Hong SM, Hruban RH, Goggins M. MicroRNA alterations of pancreatic intraepithelial neoplasias. Clin Cancer Res. 2012;18(4):981.PubMedCrossRef
30.
go back to reference Permuth-Wey J, Chen DT, Fulp WJ, Yoder SJ, Zhang Y, Georgeades C, et al. Plasma MicroRNAs as novel biomarkers for patients with Intraductal papillary mucinous neoplasms of the pancreas. Cancer Prev Res (Phila). 2015;8(9):826.CrossRef Permuth-Wey J, Chen DT, Fulp WJ, Yoder SJ, Zhang Y, Georgeades C, et al. Plasma MicroRNAs as novel biomarkers for patients with Intraductal papillary mucinous neoplasms of the pancreas. Cancer Prev Res (Phila). 2015;8(9):826.CrossRef
31.
go back to reference Thorns C, Schurmann C, Gebauer N, Wallaschofski H, Kumpers C, Bernard V, et al. Global microRNA profiling of pancreatic neuroendocrine neoplasias. Anticancer Res. 2014;34(5):2249.PubMed Thorns C, Schurmann C, Gebauer N, Wallaschofski H, Kumpers C, Bernard V, et al. Global microRNA profiling of pancreatic neuroendocrine neoplasias. Anticancer Res. 2014;34(5):2249.PubMed
32.
go back to reference Sandhu V, Bowitz Lothe IM, Labori KJ, Lingjaerde OC, Buanes T, Dalsgaard AM, et al. Molecular signatures of mRNAs and miRNAs as prognostic biomarkers in pancreatobiliary and intestinal types of periampullary adenocarcinomas. Mol Oncol. 2015;9(4):758.PubMedCrossRef Sandhu V, Bowitz Lothe IM, Labori KJ, Lingjaerde OC, Buanes T, Dalsgaard AM, et al. Molecular signatures of mRNAs and miRNAs as prognostic biomarkers in pancreatobiliary and intestinal types of periampullary adenocarcinomas. Mol Oncol. 2015;9(4):758.PubMedCrossRef
33.
go back to reference Casadei L, Calore F, Creighton CJ, Guescini M, Batte K, Iwenofu OH, et al. Exosome-derived miR-25-3p and miR-92a-3p stimulate Liposarcoma progression. Cancer Res. 2017;77(14):3846.PubMedPubMedCentralCrossRef Casadei L, Calore F, Creighton CJ, Guescini M, Batte K, Iwenofu OH, et al. Exosome-derived miR-25-3p and miR-92a-3p stimulate Liposarcoma progression. Cancer Res. 2017;77(14):3846.PubMedPubMedCentralCrossRef
34.
go back to reference Drusco A, Fadda P, Nigita G, Fassan M, Bottoni A, Gardiman MP, et al. Circulating Micrornas Predict Survival of Patients with Tumors of Glial Origin. EBioMedicine. 2018;30:105.PubMedCrossRef Drusco A, Fadda P, Nigita G, Fassan M, Bottoni A, Gardiman MP, et al. Circulating Micrornas Predict Survival of Patients with Tumors of Glial Origin. EBioMedicine. 2018;30:105.PubMedCrossRef
35.
go back to reference Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc Series B. 1995;57:289-300. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc Series B. 1995;57:289-300.
36.
go back to reference Carotenuto P, Fassan M, Pandolfo R, Lampis A, Vicentini C, Cascione L, et al. Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers. Gut. 2017;66(7):1268.PubMedCrossRef Carotenuto P, Fassan M, Pandolfo R, Lampis A, Vicentini C, Cascione L, et al. Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers. Gut. 2017;66(7):1268.PubMedCrossRef
37.
go back to reference Berindan-Neagoe I, Monroig Pdel C, Pasculli B, Calin GA. MicroRNAome genome: a treasure for cancer diagnosis and therapy. CA Cancer J Clin. 2014;64(5):311.PubMedPubMedCentralCrossRef Berindan-Neagoe I, Monroig Pdel C, Pasculli B, Calin GA. MicroRNAome genome: a treasure for cancer diagnosis and therapy. CA Cancer J Clin. 2014;64(5):311.PubMedPubMedCentralCrossRef
38.
go back to reference Hollis M, Nair K, Vyas A, Chaturvedi LS, Gambhir S, Vyas D. MicroRNAs potential utility in colon cancer: early detection, prognosis, and chemosensitivity. World J Gastroenterol. 2015;21(27):8284.PubMedPubMedCentralCrossRef Hollis M, Nair K, Vyas A, Chaturvedi LS, Gambhir S, Vyas D. MicroRNAs potential utility in colon cancer: early detection, prognosis, and chemosensitivity. World J Gastroenterol. 2015;21(27):8284.PubMedPubMedCentralCrossRef
39.
go back to reference Jamieson NB, Morran DC, Morton JP, Ali A, Dickson EJ, Carter CR, et al. MicroRNA molecular profiles associated with diagnosis, clinicopathologic criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinoma. Clin Cancer Res. 2012;18(2):534.PubMedCrossRef Jamieson NB, Morran DC, Morton JP, Ali A, Dickson EJ, Carter CR, et al. MicroRNA molecular profiles associated with diagnosis, clinicopathologic criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinoma. Clin Cancer Res. 2012;18(2):534.PubMedCrossRef
40.
go back to reference Giovannetti E, Funel N, Peters GJ, Del Chiaro M, Erozenci LA, Vasile E, et al. MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. Cancer Res. 2010;70(11):4528.PubMedCrossRef Giovannetti E, Funel N, Peters GJ, Del Chiaro M, Erozenci LA, Vasile E, et al. MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. Cancer Res. 2010;70(11):4528.PubMedCrossRef
41.
go back to reference Papaconstantinou IG, Manta A, Gazouli M, Lyberopoulou A, Lykoudis PM, Polymeneas G, et al. Expression of microRNAs in patients with pancreatic cancer and its prognostic significance. Pancreas. 2013;42(1):67.PubMedCrossRef Papaconstantinou IG, Manta A, Gazouli M, Lyberopoulou A, Lykoudis PM, Polymeneas G, et al. Expression of microRNAs in patients with pancreatic cancer and its prognostic significance. Pancreas. 2013;42(1):67.PubMedCrossRef
42.
go back to reference Giovannetti E, van der Velde A, Funel N, Vasile E, Perrone V, Leon LG, et al. High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer. PLoS One. 2012;7(11):e49145.PubMedPubMedCentralCrossRef Giovannetti E, van der Velde A, Funel N, Vasile E, Perrone V, Leon LG, et al. High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer. PLoS One. 2012;7(11):e49145.PubMedPubMedCentralCrossRef
43.
go back to reference Vila-Navarro E, Vila-Casadesus M, Moreira L, Duran-Sanchon S, Sinha R, Gines A, et al. MicroRNAs for detection of pancreatic Neoplasia: biomarker discovery by next-generation sequencing and validation in 2 independent cohorts. Ann Surg. 2017;265(6):1226.PubMedCrossRef Vila-Navarro E, Vila-Casadesus M, Moreira L, Duran-Sanchon S, Sinha R, Gines A, et al. MicroRNAs for detection of pancreatic Neoplasia: biomarker discovery by next-generation sequencing and validation in 2 independent cohorts. Ann Surg. 2017;265(6):1226.PubMedCrossRef
44.
go back to reference Schultz NA, Dehlendorff C, Jensen BV, Bjerregaard JK, Nielsen KR, Bojesen SE, et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA. 2014;311(4):392.PubMedCrossRef Schultz NA, Dehlendorff C, Jensen BV, Bjerregaard JK, Nielsen KR, Bojesen SE, et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA. 2014;311(4):392.PubMedCrossRef
45.
go back to reference Ganepola GA, Rutledge JR, Suman P, Yiengpruksawan A, Chang DH. Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer. World J Gastrointest Oncol. 2014;6(1):22.PubMedPubMedCentralCrossRef Ganepola GA, Rutledge JR, Suman P, Yiengpruksawan A, Chang DH. Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer. World J Gastrointest Oncol. 2014;6(1):22.PubMedPubMedCentralCrossRef
46.
go back to reference Wang J, Raimondo M, Guha S, Chen J, Diao L, Dong X, et al. Circulating microRNAs in pancreatic juice as candidate biomarkers of pancreatic Cancer. J Cancer. 2014;5(8):696.PubMedPubMedCentralCrossRef Wang J, Raimondo M, Guha S, Chen J, Diao L, Dong X, et al. Circulating microRNAs in pancreatic juice as candidate biomarkers of pancreatic Cancer. J Cancer. 2014;5(8):696.PubMedPubMedCentralCrossRef
47.
go back to reference Liu R, Chen X, Du Y, Yao W, Shen L, Wang C, et al. Serum microRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer. Clin Chem. 2012;58(3):610.PubMedCrossRef Liu R, Chen X, Du Y, Yao W, Shen L, Wang C, et al. Serum microRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer. Clin Chem. 2012;58(3):610.PubMedCrossRef
48.
go back to reference Kong X, Du Y, Wang G, Gao J, Gong Y, Li L, et al. Detection of differentially expressed microRNAs in serum of pancreatic ductal adenocarcinoma patients: miR-196a could be a potential marker for poor prognosis. Dig Dis Sci. 2011;56(2):602.PubMedCrossRef Kong X, Du Y, Wang G, Gao J, Gong Y, Li L, et al. Detection of differentially expressed microRNAs in serum of pancreatic ductal adenocarcinoma patients: miR-196a could be a potential marker for poor prognosis. Dig Dis Sci. 2011;56(2):602.PubMedCrossRef
49.
go back to reference Kishikawa T, Otsuka M, Ohno M, Yoshikawa T, Takata A, Koike K. Circulating RNAs as new biomarkers for detecting pancreatic cancer. World J Gastroenterol. 2015;21(28):8527.PubMedPubMedCentralCrossRef Kishikawa T, Otsuka M, Ohno M, Yoshikawa T, Takata A, Koike K. Circulating RNAs as new biomarkers for detecting pancreatic cancer. World J Gastroenterol. 2015;21(28):8527.PubMedPubMedCentralCrossRef
50.
go back to reference Ruebel K, Leontovich AA, Stilling GA, Zhang S, Righi A, Jin L, et al. MicroRNA expression in ileal carcinoid tumors: downregulation of microRNA-133a with tumor progression. Mod Pathol. 2010;23(3):367.PubMedCrossRef Ruebel K, Leontovich AA, Stilling GA, Zhang S, Righi A, Jin L, et al. MicroRNA expression in ileal carcinoid tumors: downregulation of microRNA-133a with tumor progression. Mod Pathol. 2010;23(3):367.PubMedCrossRef
51.
go back to reference Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol. 2006;24(29):4677.PubMedCrossRef Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol. 2006;24(29):4677.PubMedCrossRef
52.
go back to reference Li SC, Essaghir A, Martijn C, Lloyd RV, Demoulin JB, Oberg K, et al. Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors. Mod Pathol. 2013;26(5):685.PubMedPubMedCentralCrossRef Li SC, Essaghir A, Martijn C, Lloyd RV, Demoulin JB, Oberg K, et al. Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors. Mod Pathol. 2013;26(5):685.PubMedPubMedCentralCrossRef
53.
go back to reference Permuth-Wey J, Chen YA, Fisher K, McCarthy S, Qu X, Lloyd MC, et al. A genome-wide investigation of microRNA expression identifies biologically-meaningful microRNAs that distinguish between high-risk and low-risk intraductal papillary mucinous neoplasms of the pancreas. PLoS One. 2015;10(1):e0116869.PubMedPubMedCentralCrossRef Permuth-Wey J, Chen YA, Fisher K, McCarthy S, Qu X, Lloyd MC, et al. A genome-wide investigation of microRNA expression identifies biologically-meaningful microRNAs that distinguish between high-risk and low-risk intraductal papillary mucinous neoplasms of the pancreas. PLoS One. 2015;10(1):e0116869.PubMedPubMedCentralCrossRef
54.
go back to reference Lubezky N, Loewenstein S, Ben-Haim M, Brazowski E, Marmor S, Pasmanik-Chor M, et al. MicroRNA expression signatures in intraductal papillary mucinous neoplasm of the pancreas. Surgery. 2013;153(5):663.PubMedCrossRef Lubezky N, Loewenstein S, Ben-Haim M, Brazowski E, Marmor S, Pasmanik-Chor M, et al. MicroRNA expression signatures in intraductal papillary mucinous neoplasm of the pancreas. Surgery. 2013;153(5):663.PubMedCrossRef
55.
go back to reference Caponi S, Funel N, Frampton AE, Mosca F, Santarpia L, Van der Velde AG, et al. The good, the bad and the ugly: a tale of miR-101, miR-21 and miR-155 in pancreatic intraductal papillary mucinous neoplasms. Ann Oncol. 2013;24(3):734.PubMedCrossRef Caponi S, Funel N, Frampton AE, Mosca F, Santarpia L, Van der Velde AG, et al. The good, the bad and the ugly: a tale of miR-101, miR-21 and miR-155 in pancreatic intraductal papillary mucinous neoplasms. Ann Oncol. 2013;24(3):734.PubMedCrossRef
56.
57.
go back to reference Murali Manohar K, Sasikala M, Kvsrr Y, Sunil V, Talukdar R, Murthy H, et al. Plasma microRNA192 in combination with serum CA19-9 as non-invasive prognostic biomarker in periampullary carcinoma. Tumour Biol. 2017;39(3):1010428317695018.PubMedCrossRef Murali Manohar K, Sasikala M, Kvsrr Y, Sunil V, Talukdar R, Murthy H, et al. Plasma microRNA192 in combination with serum CA19-9 as non-invasive prognostic biomarker in periampullary carcinoma. Tumour Biol. 2017;39(3):1010428317695018.PubMedCrossRef
59.
go back to reference Cheng L, Sharples RA, Scicluna BJ, Hill AF. Exosomes provide a protective and enriched source of miRNA for biomarker profiling compared to intracellular and cell-free blood. J Extracell Vesicles. 2014;3. Cheng L, Sharples RA, Scicluna BJ, Hill AF. Exosomes provide a protective and enriched source of miRNA for biomarker profiling compared to intracellular and cell-free blood. J Extracell Vesicles. 2014;3.
61.
go back to reference Zheng J, Yu L, Chen W, Lu X, Fan X. Circulating exosomal microRNAs reveal the mechanism of Fructus Meliae Toosendan-induced liver injury in mice. Sci Rep. 2018;8(1):2832.PubMedPubMedCentralCrossRef Zheng J, Yu L, Chen W, Lu X, Fan X. Circulating exosomal microRNAs reveal the mechanism of Fructus Meliae Toosendan-induced liver injury in mice. Sci Rep. 2018;8(1):2832.PubMedPubMedCentralCrossRef
62.
go back to reference Ogata-Kawata H, Izumiya M, Kurioka D, Honma Y, Yamada Y, Furuta K, et al. Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One. 2014;9(4):e92921.PubMedPubMedCentralCrossRef Ogata-Kawata H, Izumiya M, Kurioka D, Honma Y, Yamada Y, Furuta K, et al. Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One. 2014;9(4):e92921.PubMedPubMedCentralCrossRef
63.
go back to reference Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 2008;110(1):13.PubMedCrossRef Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 2008;110(1):13.PubMedCrossRef
64.
go back to reference Andre F, Schartz NE, Movassagh M, Flament C, Pautier P, Morice P, et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet. 2002;360(9329):295.PubMedCrossRef Andre F, Schartz NE, Movassagh M, Flament C, Pautier P, Morice P, et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet. 2002;360(9329):295.PubMedCrossRef
65.
go back to reference Armstrong DA, Nymon AB, Ringelberg CS, Lesseur C, Hazlett HF, Howard L, et al. Pulmonary microRNA profiling: implications in upper lobe predominant lung disease. Clin Epigenetics. 2017;9:56.PubMedPubMedCentralCrossRef Armstrong DA, Nymon AB, Ringelberg CS, Lesseur C, Hazlett HF, Howard L, et al. Pulmonary microRNA profiling: implications in upper lobe predominant lung disease. Clin Epigenetics. 2017;9:56.PubMedPubMedCentralCrossRef
66.
go back to reference Nakamura A, Rampersaud YR, Sharma A, Lewis SJ, Wu B, Datta P, et al. Identification of microRNA-181a-5p and microRNA-4454 as mediators of facet cartilage degeneration. JCI Insight. 2016;1(12):e86820.PubMedPubMedCentralCrossRef Nakamura A, Rampersaud YR, Sharma A, Lewis SJ, Wu B, Datta P, et al. Identification of microRNA-181a-5p and microRNA-4454 as mediators of facet cartilage degeneration. JCI Insight. 2016;1(12):e86820.PubMedPubMedCentralCrossRef
67.
go back to reference Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK, et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol. 2015;17(6):816.PubMedPubMedCentralCrossRef Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK, et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol. 2015;17(6):816.PubMedPubMedCentralCrossRef
68.
go back to reference Charrier A, Chen R, Chen L, Kemper S, Hattori T, Takigawa M, et al. Connective tissue growth factor (CCN2) and microRNA-21 are components of a positive feedback loop in pancreatic stellate cells (PSC) during chronic pancreatitis and are exported in PSC-derived exosomes. J Cell Commun Signal. 2014;8(2):147.PubMedPubMedCentralCrossRef Charrier A, Chen R, Chen L, Kemper S, Hattori T, Takigawa M, et al. Connective tissue growth factor (CCN2) and microRNA-21 are components of a positive feedback loop in pancreatic stellate cells (PSC) during chronic pancreatitis and are exported in PSC-derived exosomes. J Cell Commun Signal. 2014;8(2):147.PubMedPubMedCentralCrossRef
69.
go back to reference Westgaard A, Tafjord S, Farstad IN, Cvancarova M, Eide TJ, Mathisen O, et al. Pancreatobiliary versus intestinal histologic type of differentiation is an independent prognostic factor in resected periampullary adenocarcinoma. BMC Cancer. 2008;8:170.PubMedPubMedCentralCrossRef Westgaard A, Tafjord S, Farstad IN, Cvancarova M, Eide TJ, Mathisen O, et al. Pancreatobiliary versus intestinal histologic type of differentiation is an independent prognostic factor in resected periampullary adenocarcinoma. BMC Cancer. 2008;8:170.PubMedPubMedCentralCrossRef
70.
go back to reference Zhou H, Schaefer N, Wolff M, Fischer HP. Carcinoma of the ampulla of Vater: comparative histologic/immunohistochemical classification and follow-up. Am J Surg Pathol. 2004;28(7):875.PubMedCrossRef Zhou H, Schaefer N, Wolff M, Fischer HP. Carcinoma of the ampulla of Vater: comparative histologic/immunohistochemical classification and follow-up. Am J Surg Pathol. 2004;28(7):875.PubMedCrossRef
71.
go back to reference Sohn TA, Yeo CJ, Cameron JL, Hruban RH, Fukushima N, Campbell KA, et al. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann Surg. 2004;239(6):788.PubMedPubMedCentralCrossRef Sohn TA, Yeo CJ, Cameron JL, Hruban RH, Fukushima N, Campbell KA, et al. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann Surg. 2004;239(6):788.PubMedPubMedCentralCrossRef
Metadata
Title
Exosomal miRNA signatures of pancreatic lesions
Authors
Caterina Vicentini
Federica Calore
Giovanni Nigita
Paolo Fadda
Michele Simbolo
Nicola Sperandio
Claudio Luchini
Rita T. Lawlor
Carlo Maria Croce
Vincenzo Corbo
Matteo Fassan
Aldo Scarpa
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2020
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-020-01287-y

Other articles of this Issue 1/2020

BMC Gastroenterology 1/2020 Go to the issue