Can miRNA Biomarkers Be Utilized to Improve the Evaluation and Management of Pancreatic Cystic Lesions?

• Authors: Linda S. Lee , Anna E. Szafranska-Schwarzbach , Bernard F. Andruss , Darwin L. Conwell
• Languages of publication: EN

Abstracts

EN

This article reviews the current strategies and challenges of diagnosing pancreatic cystic lesions, and presents an overview of molecular tools that are available to enhance diagnostic accuracy. Specifically, we highlight the emergence of microRNAs (miRNAs) as diagnostic markers. miRNA signatures have been reported for both solid tissue and biofluid specimens, including cyst fluid, collected from patients with solid and cystic pancreatic lesions. These miRNA signatures offer the opportunity to improve molecular characterization of pancreatic lesions, to help guide clinical management through early diagnosis and informed prognosis, and to provide novel therapeutic targets for pancreatic cancer.

Keywords

EN

microRNA; miRNAs; pancreatic cystic neoplasms; cystic fluid; Laboratory Developed Test (LDT); Clinical Laboratory Improvement Amendments (CLIA); College of American Pathologists (CAP); mucinous cystic neoplasms (MCN); intraductal papillary mucinous neoplasms (IPMN); cystadenomas (SCA); solid pseudopapillary neoplasm (SPEN); endoscopic ultrasound (EUS)

• Publisher: De Gruyter Open
• Journal: microRNA Diagnostics and Therapeutics
• Year: 2014
• Volume: 1
• Issue: 1

Dates

published

1 - 1 - 2014

accepted

14 - 7 - 2013

received

3 - 6 - 2013

online

7 - 10 - 2013

Contributors

author

Linda S. Lee

• Brigham and Women’s Hospital, Boston, MA

author

Anna E. Szafranska-Schwarzbach

• Asuragen Inc., Austin, TX

author

Bernard F. Andruss

• Asuragen Inc., Austin, TX

author

Darwin L. Conwell

• Brigham and Women’s Hospital, Boston, MA

References

• [1] Megibow AJ, Baker ME, Gore RM, Taylor A. The incidental pancreatic cyst. Radiol Clin North Am. 2011; 49, 349-359.[Crossref]
• [2] Lee KS, Sekhar A, Rofsky NM, Pedrosa I. Prevalence of incidental pancreatic cysts in the adult population on MR imaging. Am J Gastroenterol. 2010; 105, 2079-2084.[Crossref]
• [3] Lee LS, Szafranska-Schwarzbach AE, Wylie D, Bellizzi AM, Doyle LA, Kadiyala V, Suleiman S, Banks PA, Andruss BF, Conwell DL. Investigation of microRNA (miRNA) in pancreatic cystic tumors (IMPACT) study: Differential expression observed among pancreatic cystic neoplasms. Pancreatology. 2013; 13, e47-e48.[Crossref]
• [4] Lee LS. Evaluation and Management of Pancreatic Cystic Lesions. J Clin Outcomes Management. 2013; 20, 129-142.
• [5] Khalid A, Brugge W. ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts. Am J Gastroenterol. 2007; 102, 2339-2349.[Crossref]
• [6] Al-Haddad M, Schmidt MC, Sandrasegaran K, Dewitt J. Diagnosis and treatment of cystic pancreatic tumors. Clin Gastroenterol Hepatol. 2011; 9, 635-648.
• [7] Maker AV, Lee LS, Raut CP, Clancy TE, Swanson RS. Cytology from pancreatic cysts has marginal utility in surgical decision-making. Ann Surg Oncol. 2008; 15, 3187-3192.[Crossref]
• [8] Simeone DM. SSAT/AGA/ASGE state of the art conference on cystic neoplasms of the pancreas. J Gastrointest Surg. 2008; 12, 1475-1477.[Crossref]
• [9] Andren-Sandberg A, Dervenis C. Pancreatic pseudocysts in the 21st century. Part II: natural history. JOP. 2004; 5, 64-70.
• [10] Sakorafas GH, Smyrniotis V, Reid-Lombardo KM, Sarr MG. Primary pancreatic cystic neoplasms revisited: part II. Mucinous cystic neoplasms. Surg Oncol. 2011; 20, e93-101.[Crossref]
• [11] Bramis K, Petrou A, Papalambros A, Manzelli A, Mantonakis E, Brennan N, Felekouras E. Serous cystadenocarcinoma of the pancreas: report of a case and management reflections. World J Surg Oncol. 2012; 10, 51.[Crossref]
• [12] Katz MH, Mortenson MM, Wang H, Hwang R, Tamm EP, Staerkel G, Lee JH, Evans DB, Fleming JB. Diagnosis and management of cystic neoplasms of the pancreas: an evidencebased approach. J Am Coll Surg. 2008; 207, 106-120.[Crossref]
• [13] Tseng JF. Management of serous cystadenoma of the pancreas. J Gastrointest Surg. 2008; 12, 408-410.[Crossref]
• [14] Wargo JA, Fernandez-del-Castillo C, Warshaw AL. Management of pancreatic serous cystadenomas. Adv Surg. 2009; 43, 23-34.[Crossref]
• [15] Crippa S, Salvia R, Warshaw AL, Dominguez I, Bassi C, Falconi M, Thayer SP, Zamboni G, Lauwers GY, Mino-Kenudson M, et al. Mucinous cystic neoplasm of the pancreas is not an aggressive entity: lessons from 163 resected patients. Ann Surg. 2008; 247, 571-579.
• [16] Tanaka M, Fernandez-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, Kimura W, Levy P, Pitman MB, Schmidt CM, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012; 12, 183-197.[Crossref]
• [17] Furukawa T, Kloppel G, Volkan Adsay N, Albores-Saavedra J, Fukushima N, Horii A, Hruban RH, Kato Y, Klimstra DS, Longnecker DS, et al. Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study. Virchows Arch. 2005; 447, 794-799.[Crossref]
• [18] Bournet B, Kirzin S, Carrere N, Portier G, Otal P, Selves J, Musso C, Suc B, Moreau J, Fourtanier G, et al. Clinical fate of branch duct and mixed forms of intraductal papillary mucinous neoplasia of the pancreas. J Gastroenterol Hepatol. 2009; 24, 1211-1217.[Crossref]
• [19] Levy P, Jouannaud V, O’Toole D, Couvelard A, Vullierme MP, Palazzo L, Aubert A, Ponsot P, Sauvanet A, Maire F, et al. Natural history of intraductal papillary mucinous tumors of the pancreas: actuarial risk of malignancy. Clin Gastroenterol Hepatol. 2006; 4, 460-468.[Crossref]
• [20] Tanaka M, Chari S, Adsay V, Fernandez-del Castillo C, Falconi M, Shimizu M, Yamaguchi K, Yamao K, Matsuno S. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 2006; 6, 17-32.[Crossref]
• [21] Reddy S, Wolfgang CL. Solid pseudopapillary neoplasms of the pancreas. Adv Surg. 2009; 43, 269-282.[Crossref]
• [22] Frost M, Krige JE, Bornman PC, Panieri E, Beningfield SJ, Wainwright H. Solid pseudopapillary epithelial neoplasm--a rare but curable pancreatic tumour in young women. S Afr J Surg. 2011; 49, 75-76, 78-81.
• [23] Lee LS. Diagnosis of pancreatic neuroendocrine tumors and the role of endoscopic ultrasound. Gastroenterol Hepatol (N Y). 2010; 6, 520-522.
• [24] Colombo P, Arizzi C, Roncalli M. Acinar cell cystadenocarcinoma of the pancreas: report of rare case and review of the literature. Hum Pathol. 2004; 35, 1568-1571.[Crossref]
• [25] Correa-Gallego C, Ferrone CR, Thayer SP, Wargo JA, Warshaw AL, Fernandez-Del Castillo C. Incidental pancreatic cysts: do we really know what we are watching? Pancreatology. 2010; 10, 144-150.[Crossref]
• [26] Das A, Ngamruengphong S, Nagendra S, Chak A. Asymptomatic pancreatic cystic neoplasm: a costeffectiveness analysis of different strategies of management. Gastrointest Endosc. 2009; 70, 690-699 e696.[Crossref]
• [27] Berland LL, Silverman SG, Gore RM, Mayo-Smith WW, Megibow AJ, Yee J, Brink JA, Baker ME, Federle MP, Foley WD, et al. Managing incidental findings on abdominal CT: white paper of the ACR incidental findings committee. J Am Coll Radiol. 2010; 7, 754-773.[Crossref]
• [28] Waters JA, Schmidt CM, Pinchot JW, White PB, Cummings OW, Pitt HA, Sandrasegaran K, Akisik F, Howard TJ, Nakeeb A, et al. CT vs MRCP: optimal classification of IPMN type and extent. J Gastrointest Surg. 2008; 12, 101-109.[Crossref]
• [29] Sodickson A, Baeyens PF, Andriole KP, Prevedello LM, Nawfel RD, Hanson R, Khorasani R. Recurrent CT, cumulative radiation exposure, and associated radiation-induced cancer risks from CT of adults. Radiology. 2009; 251, 175-184.[Crossref]
• [30] Procacci C, Biasiutti C, Carbognin G, Accordini S, Bicego E, Guarise A, Spoto E, Andreis IA, De Marco R, Megibow AJ. Characterization of cystic tumors of the pancreas: CT accuracy. J Comput Assist Tomogr. 1999; 23, 906-912.[Crossref]
• [31] Sainani NI, Saokar A, Deshpande V, Fernandez-del Castillo C, Hahn P, Sahani DV. Comparative performance of MDCT and MRI with MR cholangiopancreatography in characterizing small pancreatic cysts. AJR Am J Roentgenol. 2009; 193, 722-731.[Crossref]
• [32] Visser BC, Yeh BM, Qayyum A, Way LW, McCulloch CE, Coakley FV. Characterization of cystic pancreatic masses: relative accuracy of CT and MRI. AJR Am J Roentgenol. 2007; 189, 648-656.[Crossref]
• [33] Ogawa H, Itoh S, Ikeda M, Suzuki K, Naganawa S. Intraductal papillary mucinous neoplasm of the pancreas: assessment of the likelihood of invasiveness with multisection CT. Radiology. 2008; 248, 876-886.[Crossref]
• [34] Brugge WR, Lewandrowski K, Lee-Lewandrowski E, Centeno BA, Szydlo T, Regan S, del Castillo CF, Warshaw AL. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology. 2004; 126, 1330-1336.[Crossref]
• [35] Zhong N, Zhang L, Takahashi N, Shalmiyev V, Canto MI, Clain JE, Deutsch JC, DeWitt J, Eloubeidi MA, Gleeson FC, et al. Histologic and imaging features of mural nodules in mucinous pancreatic cysts. Clin Gastroenterol Hepatol. 2012; 10, 192-198, 198 e191-192. [Crossref]
• [36] de Jong K, van Hooft JE, Nio CY, Gouma DJ, Dijkgraaf MG, Bruno MJ, Fockens P. Accuracy of preoperative workup in a prospective series of surgically resected cystic pancreatic lesions. Scand J Gastroenterol. 2012; 47, 1056-1063.[Crossref]
• [37] Hara T, Yamaguchi T, Ishihara T, Tsuyuguchi T, Kondo F, Kato K, Asano T, Saisho H. Diagnosis and patient management of intraductal papillary-mucinous tumor of the pancreas by using peroral pancreatoscopy and intraductal ultrasonography. Gastroenterology. 2002; 122, 34-43.[Crossref]
• [38] Yamaguchi T, Shirai Y, Ishihara T, Sudo K, Nakagawa A, Ito H, Miyazaki M, Nomura F, Saisho H. Pancreatic juice cytology in the diagnosis of intraductal papillary mucinous neoplasm of the pancreas: significance of sampling by peroral pancreatoscopy. Cancer. 2005; 104, 2830-2836.[Crossref]
• [39] Itoi T, Sofuni A, Itokawa F, Kurihara T, Tsuchiya T, Ishii K, Tsuji S, Ikeuchi N, Arisaka Y, Moriyasu F. Initial experience of peroral pancreatoscopy combined with narrow-band imaging in the diagnosis of intraductal papillary mucinous neoplasms of the pancreas (with videos). Gastrointest Endosc. 2007; 66, 793-797.[Crossref]
• [40] Cheon YK, Cho YD, Jeon SR, Moon JH, Jeong SW, Hur KY, Jin SY, Lee JS. Pancreatic resection guided by preoperative intraductal ultrasonography for intraductal papillary mucinous neoplasm. Am J Gastroenterol. 2010; 105, 1963-1969.[Crossref]
• [41] Lee LS, Saltzman JR, Bounds BC, Poneros JM, Brugge WR, Thompson CC. EUS-guided fine needle aspiration of pancreatic cysts: a retrospective analysis of complications and their predictors. Clin Gastroenterol Hepatol. 2005; 3, 231-236.[Crossref]
• [42] Maire F, Couvelard A, Hammel P, Ponsot P, Palazzo L, Aubert A, Degott C, Dancour A, Felce-Dachez M, O’Toole D, et al. Intraductal papillary mucinous tumors of the pancreas: the preoperative value of cytologic and histopathologic diagnosis. Gastrointest Endosc. 2003; 58, 701-706.[Crossref]
• [43] Sedlack R, Affi A, Vazquez-Sequeiros E, Norton ID, Clain JE, Wiersema MJ. Utility of EUS in the evaluation of cystic pancreatic lesions. Gastrointest Endosc. 2002; 56, 543-547.[Crossref]
• [44] Attasaranya S, Pais S, LeBlanc J, McHenry L, Sherman S, DeWitt JM. Endoscopic ultrasound-guided fine needle aspiration and cyst fluid analysis for pancreatic cysts. JOP. 2007; 8, 553-563.
• [45] Jani N, Dewitt J, Eloubeidi M, Varadarajulu S, Appalaneni V, Hoffman B, Brugge W, Lee K, Khalid A, McGrath K. Endoscopic ultrasound-guided fine-needle aspiration for diagnosis of solid pseudopapillary tumors of the pancreas: a multicenter experience. Endoscopy. 2008; 40, 200-203.[Crossref]
• [46] van der Waaij LA, van Dullemen HM, Porte RJ. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointest Endosc. 2005; 62, 383-389.
• [47] Fritz S, Hackert T, Hinz U, Hartwig W, Buchler MW, Werner J. Role of serum carbohydrate antigen 19-9 and carcinoembryonic antigen in distinguishing between benign and invasive intraductal papillary mucinous neoplasm of the pancreas. Br J Surg. 2011; 98, 104-110. [Crossref]
• [48] Khalid A, Zahid M, Finkelstein SD, LeBlanc JK, Kaushik N, Ahmad N, Brugge WR, Edmundowicz SA, Hawes RH, McGrath KM. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest Endosc. 2009; 69, 1095-1102.[Crossref]
• [49] Bader AG. miR-34 - a microRNA replacement therapy is headed to the clinic. Frontiers in genetics. 2012; 3, 120.
• [50] Szafranska-Schwarzbach AE, Adai AT, Lee LS, Conwell DL, Andruss BF. Development of a miRNA-based diagnostic assay for pancreatic ductal adenocarcinoma. Expert review of molecular diagnostics. 2011; 11, 249-257.
• [51] Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M. MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J Gastrointest Surg. 2008; 12, 2171-2176.[Crossref]
• [52] Preis M, Gardner TB, Gordon SR, Pipas JM, Mackenzie TA, Klein EE, Longnecker DS, Gutmann EJ, Sempere LF, Korc M. MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma. Clin Cancer Res. 2011; 17, 5812-5821.
• [53] Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C, Croce CM. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. Jama. 2007; 297, 1901-1908.[Crossref]
• [54] Szafranska AE, Davison TS, John J, Cannon T, Sipos B, Maghnouj A, Labourier E, Hahn SA. MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene. 2007; 26, 4442-4452.[Crossref]
• [55] Li Y, Vandenboom TG, 2nd, Wang Z, Kong D, Ali S, Philip PA, Sarkar FH. miR-146a suppresses invasion of pancreatic cancer cells. Cancer Res. 2010; 70, 1486-1495.
• [56] Brooks EL, Preis SR, Hwang SJ, Murabito JM, Benjamin EJ, Kelly-Hayes M, Sorlie P, Levy D. Health insurance and cardiovascular disease risk factors. The American journal of medicine. 2010; 123, 741-747.[Crossref]
• [57] Zhao WG, Yu SN, Lu ZH, Ma YH, Gu YM, Chen J. The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS. Carcinogenesis. 2010; 31, 1726-1733.
• [58] Yu S, Lu Z, Liu C, Meng Y, Ma Y, Zhao W, Liu J, Yu J, Chen J. miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Res. 2010; 70, 6015-6025.
• [59] Ma Y, Yu S, Zhao W, Lu Z, Chen J. miR-27a regulates the growth, colony formation and migration of pancreatic cancer cells by targeting Sprouty2. Cancer Lett. 2010; 298, 150-158.[Crossref]
• [60] Yan H, Wu J, Liu W, Zuo Y, Chen S, Zhang S, Zeng M, Huang W. MicroRNA-20a overexpression inhibited proliferation and metastasis of pancreatic carcinoma cells. Hum Gene Ther. 2010; 21, 1723-1734.
• [61] Ji Q, Hao X, Zhang M, Tang W, Yang M, Li L, Xiang D, Desano JT, Bommer GT, Fan D, et al. MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS One. 2009; 4, e6816.
• [62] Zhang Y, Li M, Wang H, Fisher WE, Lin PH, Yao Q, Chen C. Profiling of 95 microRNAs in pancreatic cancer cell lines and surgical specimens by real-time PCR analysis. World J Surg. 2009; 33, 698-709.
• [63] Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, Morgan DL, Postier RG, Brackett DJ, Schmittgen TD. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer. 2007; 120, 1046-1054.
• [64] Munding JB, Adai AT, Maghnouj A, Urbanik A, Zollner H, Liffers ST, Chromik AM, Uhl W, Szafranska-Schwarzbach AE, Tannapfel A, et al. Global microRNA expression profiling of microdissected tissues identifies miR-135b as a novel biomarker for pancreatic ductal adenocarcinoma. Int J Cancer. 2012; 131, E86-95.[Crossref]
• [65] Greither T, Grochola LF, Udelnow A, Lautenschlager C, Wurl P, Taubert H. Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer. 2010; 126, 73-80.
• [66] Yu J, Li A, Hong SM, Hruban RH, Goggins M. MicroRNA Alterations of Pancreatic Intraepithelial Neoplasias. Clin Cancer Res. 2012; 18, 981-992.[Crossref]
• [67] Hanoun N, Delpu Y, Suriawinata AA, Bournet B, Bureau C, Selves J, Tsongalis GJ, Dufresne M, Buscail L, Cordelier P, et al. The silencing of microRNA 148a production by DNA hypermethylation is an early event in pancreatic carcinogenesis. Clin Chem. 2010; 56, 1107-1118.
• [68] Taylor B. Carcinoma of the head of the pancreas versus chronic pancreatitis: diagnostic dilemma with significant consequences. World J Surg. 2003; 27, 1249-1257.[Crossref]
• [69] Graham RA, Bankoff M, Hediger R, Shaker HZ, Reinhold RB. Fine-needle aspiration biopsy of pancreatic ductal adenocarcinoma: loss of diagnostic accuracy with small tumors. J Surg Oncol. 1994; 55, 92-94.[Crossref]
• [70] Eloubeidi MA, Chen VK, Eltoum IA, Jhala D, Chhieng DC, Jhala N, Vickers SM, Wilcox CM. Endoscopic ultrasoundguided fine needle aspiration biopsy of patients with suspected pancreatic cancer: diagnostic accuracy and acute and 30-day complications. Am J Gastroenterol. 2003; 98, 2663-2668.
• [71] Zalatnai A. [Pathologic diagnosis of pancreatic cancer--facts, pitfalls, challenges]. Orv Hetil. 2001; 142, 1885-1890.
• [72] Szafranska-Schwarzbach AE WD, Lloyd MB, Adai AT, Sanders MS, Brand RE, Lee LS, Conwell DL, Rateb G, Menard C, Morisset JA, Vignesh S, Centeno B, Hartleb M, Wiechowska-Kozlowska A, Stefanczyk L, Lefferts CL, Tsongalis GJ, Hahn S, Andruss BF. A multi-center study of a microRNA-based assay for the diagnosis of pancreatic ductal adenocarcinoma in fine needle aspirates. American Pancreatic Association Annual Meeting (2011, Chicago, IL).
• [73] Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, Xiao T, Schafer J, Lee ML, Schmittgen TD, et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS One. 2008; 3, e3694.
• [74] Michael A, Bajracharya SD, Yuen PS, Zhou H, Star RA, Illei GG, Alevizos I. Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis. 2010; 16, 34-38.[Crossref]
• [75] Dimov I, Jankovic Velickovic L, Stefanovic V. Urinary exosomes. ScientificWorldJournal. 2009; 9, 1107-1118.[Crossref]
• [76] Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT, Jr., Carter BS, Krichevsky AM, Breakefield XO. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008; 10, 1470-1476.[Crossref]
• [77] Gibbings DJ, Ciaudo C, Erhardt M, Voinnet O. Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat Cell Biol. 2009; 11, 1143-1149.[Crossref]
• [78] Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007; 9, 654-659.[Crossref]
• [79] Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, de Gruijl TD, Wurdinger T, Middeldorp JM. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A. 2010; 107, 6328-6333.[Crossref]
• [80] Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, Frazier ML, Killary AM, Sen S. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel bloodbased biomarkers of disease. Cancer Prev Res (Phila). 2009; 2, 807-813.[Crossref]
• [81] Liu J, Gao J, Du Y, Li Z, Ren Y, Gu J, Wang X, Gong Y, Wang W, Kong X. Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer. Int J Cancer. 2012; 131, 683-691.[Crossref]
• [82] Kong X, Du Y, Wang G, Gao J, Gong Y, Li L, Zhang Z, Zhu J, Jing Q, Qin Y, et al. Detection of differentially expressed microRNAs in serum of pancreatic ductal adenocarcinoma patients: miR-196a could be a potential marker for poor prognosis. Digestive diseases and sciences. 2011; 56, 602-609.
• [83] Brase JC, Wuttig D, Kuner R, Sultmann H. Serum microRNAs as non-invasive biomarkers for cancer. Mol Cancer. 2010; 9, 306.[Crossref]
• [84] Park JK, Lee EJ, Esau C, Schmittgen TD. Antisense inhibition of microRNA-21 or -221 arrests cell cycle, induces apoptosis, and sensitizes the effects of gemcitabine in pancreatic adenocarcinoma. Pancreas. 2009; 38, e190-199.
• [85] Moriyama T, Ohuchida K, Mizumoto K, Yu J, Sato N, Nabae T, Takahata S, Toma H, Nagai E, Tanaka M. MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance. Mol Cancer Ther. 2009; 8, 1067-1074.[Crossref]
• [86] Giovannetti E, Funel N, Peters GJ, Del Chiaro M, Erozenci LA, Vasile E, Leon LG, Pollina LE, Groen A, Falcone A, 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, 4528-4538.[Crossref]
• [87] Hwang JH, Voortman J, Giovannetti E, Steinberg SM, Leon LG, Kim YT, Funel N, Park JK, Kim MA, Kang GH, et al. Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer. PLoS One. 2010; 5, e10630.
• [88] Papaconstantinou IG, Lykoudis PM, Gazouli M, Manta A, Polymeneas G, Voros D. A review on the role of microRNA in biology, diagnosis, and treatment of pancreatic adenocarcinoma. Pancreas. 2012; 41, 671-677.[Crossref]
• [89] Tavano F, di Mola FF, Piepoli A, Panza A, Copetti M, Burbaci FP, Latiano T, Pellegrini F, Maiello E, Andriulli A, et al. Changes in miR-143 and miR-21 expression and clinicopathological correlations in pancreatic cancers. Pancreas. 2012; 41, 1280-1284.
• [90] Steele CW, Oien KA, McKay CJ, Jamieson NB. Clinical potential of microRNAs in pancreatic ductal adenocarcinoma. Pancreas. 2011; 40, 1165-1171.[Crossref]
• [91] Habbe N, Koorstra JB, Mendell JT, Offerhaus GJ, Ryu JK, Feldmann G, Mullendore ME, Goggins MG, Hong SM, Maitra A. MicroRNA miR-155 is a biomarker of early pancreatic neoplasia. Cancer Biol Ther. 2009; 8, 340-346.
• [92] Ryu JK, Matthaei H, Dal Molin M, Hong SM, Canto MI, Schulick RD, Wolfgang C, Goggins MG, Hruban RH, Cope L, et al. Elevated microRNA miR-21 levels in pancreatic cyst fluid are predictive of mucinous precursor lesions of ductal adenocarcinoma. Pancreatology. 2011; 11, 343-350.[Crossref]
• [93] Matthaei H, Wylie D, Lloyd MB, Dal Molin M, Kemppainen J, Mayo SC, Wolfgang CL, Schulick RD, Langfield L, Andruss BF, et al. miRNA Biomarkers in Cyst Fluid Augment the Diagnosis and Management of Pancreatic Cysts. Clin Cancer Res. 2012; 18, 4713-4724.[Crossref]
• [94] Jiao LR, Frampton AE, Jacob J, Pellegrino L, Krell J, Giamas G, Tsim N, Vlavianos P, Cohen P, Ahmad R, et al. MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors. PLoS One. 2012; 7, e32068.
• [95] Park YG, Lee KH, Lee JK, Lee KT, Choi DW, Choi SH, Heo JS, Jang KT, Lee EM, Kim JO, et al. [MicroRNA expression pattern in intraductal papillary mucinous neoplasm]. Korean J Gastroenterol. 2011; 58, 190-200. [Crossref]

Identifiers

DOI

10.2478/micrnat-2013-0003