MicroRNA Array Analysis Finds Elevated Serum miR-1290 Accurately Distinguishes Patients with Low-Stage Pancreatic Cancer from Healthy and Disease Controls

Clinical Cancer Research - Tập 19 Số 13 - Trang 3600-3610 - 2013
Ang Li1, Jun Yu1, Haeryoung Kim1, Christopher L. Wolfgang1, Marcia I. Canto1, Ralph H. Hruban1, Michael Goggins1
1Authors' Affiliations: Departments of 1Pathology, 2Surgery, 3Medicine, and 4Oncology, the Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, Maryland

Tóm tắt

AbstractPurpose: Our goal was to identify circulating micro RNA (miRNA) levels that could distinguish patients with low-stage pancreatic cancer from healthy and disease controls.Experimental Design: We measured 735 miRNAs in pancreatic cancer case and control sera by QRTPCR using TaqMan MicroRNA Arrays. After array analysis, we selected 18 miRNA candidates for validation in an independent set of cases and control samples.Results: Of the significantly elevated circulating miRNAs in patients with pancreatic cancer compared with controls, miR-1290 had the best diagnostic performance: receiver operating characteristic (ROC) analysis on miR-1290 serum level yielded curve areas (AUC) of 0.96 [95% confidence interval (CI), 0.91–1.00], 0.81 (0.71–0.91), and 0.80 (0.67–0.93), for subjects with pancreatic cancer (n = 41) relative to healthy controls (n = 19), subjects with chronic pancreatitis (n = 35), and pancreatic neuroendocrine tumors (n = 18), respectively. Serum miR-1290 levels were also significantly higher than healthy controls among patients with intraductal papillary mucinous neoplasm (IPMN; n = 20; AUC = 0.76, 0.61–0.91). Serum miR-1290 levels distinguished patients with low-stage pancreatic cancer from controls better than CA19-9 levels, and like CA19-9, higher miR-1290 levels predicted poorer outcome among patients undergoing pancreaticoduodenectomy. Greater numbers of miR-1290 transcripts were detected by FISH in primary pancreatic cancer and IPMN than normal pancreatic duct cells. miR-1290 influenced in vitro pancreatic cancer cell proliferation and invasive ability. Several other circulating miRNAs distinguished sera of patients with pancreatic cancer from those of healthy controls with AUCs >0.7, including miR-24, miR-134, miR-146a, miR-378, miR-484, miR-628-3p, and miR-1825.Conclusions: The detection of elevated circulating miR-1290 has the potential to improve the early detection of pancreatic cancer. Clin Cancer Res; 19(13); 3600–10. ©2013 AACR.

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Tài liệu tham khảo

Siegel, 2012, Cancer statistics, 2012, CA Cancer J Clin, 62, 10, 10.3322/caac.20138

Winter, 2006, 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience, J Gastrointest Surg, 10, 1199, 10.1016/j.gassur.2006.08.018

Vincent, 2011, Pancreatic cancer, Lancet, 378, 607, 10.1016/S0140-6736(10)62307-0

Canto, 2012, Frequent detection of pancreatic lesions in asymptomatic high-risk individuals, Gastroenterology, 142, 796, 10.1053/j.gastro.2012.01.005

Ludwig, 2011, Feasibility and yield of screening in relatives from familial pancreatic cancer families, Am J Gastroenterol, 106, 946, 10.1038/ajg.2011.65

Verna, 2010, Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strategy of imaging and genetics, Clin Cancer Res, 16, 5028, 10.1158/1078-0432.CCR-09-3209

Langer, 2009, Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer, Gut, 58, 1410, 10.1136/gut.2008.171611

Canto, 2006, Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study, Clin Gastroenterol Hepatol, 4, 766, 10.1016/j.cgh.2006.02.005

Canto, 2004, Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach, Clin Gastroenterol Hepatol, 2, 606, 10.1016/S1542-3565(04)00244-7

Brentnall, 1999, Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer, Ann Intern Med, 131, 247, 10.7326/0003-4819-131-4-199908170-00003

Poley, 2009, The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer, Am J Gastroenterol, 104, 2175, 10.1038/ajg.2009.276

Canto, 2013, International Consensus Recommendations on the management of patients with increased risk for familial pancreatic cancer (The Cancer of the Pancreas Screening (CAPS) Consortium Summit), Gut, 62, 339, 10.1136/gutjnl-2012-303108

Harsha, 2009, A compendium of potential biomarkers of pancreatic cancer, PLoS Med, 6, e1000046, 10.1371/journal.pmed.1000046

Gold, 2010, Detection of early-stage pancreatic adenocarcinoma, Cancer Epidemiol Biomarkers Prev, 19, 2786, 10.1158/1055-9965.EPI-10-0667

Brand, 2011, Serum biomarker panels for the detection of pancreatic cancer, Clin Cancer Res, 17, 805, 10.1158/1078-0432.CCR-10-0248

Koopmann, 2006, Serum markers in patients with resectable pancreatic adenocarcinoma: MIC-1 vs. CA19-9, Clin Cancer Res, 15, 442, 10.1158/1078-0432.CCR-05-0564

Kanda, 2012 17, Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts, Gut

Matsubayashi, 2006, DNA methylation alterations in the pancreatic juice of patients with suspected pancreatic disease, Cancer Res, 66, 1208, 10.1158/0008-5472.CAN-05-2664

Wu, 2011, Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development, Sci Transl Med, 3, 92ra66, 10.1126/scitranslmed.3002543

Mitchell, 2008, Circulating microRNAs as stable blood-based markers for cancer detection, Proc Natl Acad Sci U S A, 105, 10513, 10.1073/pnas.0804549105

Wang, 2009, MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease, Cancer Prev Res (Phila), 2, 807, 10.1158/1940-6207.CAPR-09-0094

Bauer, 2012, Diagnosis of pancreatic ductal adenocarcinoma and chronic pancreatitis by measurement of microRNA abundance in blood and tissue, PLoS ONE, 7, e34151, 10.1371/journal.pone.0034151

Dillhoff, 2008, MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival, J Gastrointest Surg, 12, 2171, 10.1007/s11605-008-0584-x

Bloomston, 2007, MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis, JAMA, 297, 1901, 10.1001/jama.297.17.1901

Habbe, 2009, MicroRNA miR-155 is a biomarker of early pancreatic neoplasia, Cancer Biol Ther, 8, 340, 10.4161/cbt.8.4.7338

Ryu, 2010, Aberrant MicroRNA-155 expression is an early event in the multistep progression of pancreatic adenocarcinoma, Pancreatology, 10, 66, 10.1159/000231984

Li, miR-146a suppresses invasion of pancreatic cancer cells, Cancer Res, 70, 1486, 10.1158/0008-5472.CAN-09-2792

Szafranska, 2008, Analysis of microRNAs in pancreatic fine-needle aspirates can classify benign and malignant tissues, Clin Chem, 54, 1716, 10.1373/clinchem.2008.109603

Yu, 2012, MicroRNA alterations of pancreatic intraepithelial neoplasias, Clin Cancer Res, 18, 981, 10.1158/1078-0432.CCR-11-2347

Kent, 2009, A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells, Cancer Biol Ther, 8, 2013, 10.4161/cbt.8.21.9685

Li, 2010, Pancreatic cancers epigenetically silence SIP1 and hypomethylate and overexpress miR-200a/200b in association with elevated circulating miR-200a and miR-200b levels, Cancer Res, 70, 5226, 10.1158/0008-5472.CAN-09-4227

Yu, 2010, MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation, Mol Cancer, 9, 169, 10.1186/1476-4598-9-169

Morimura, 2011, Novel diagnostic value of circulating miR-18a in plasma of patients with pancreatic cancer, Br J Cancer, 105, 1733, 10.1038/bjc.2011.453

Munding, 2012, Global microRNA expression profiling of microdissected tissues identifies miR-135b as a novel biomarker for pancreatic ductal adenocarcinoma, Int J Cancer, 131, E86, 10.1002/ijc.26466

Szafranska, 2007, MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma, Oncogene, 26, 4442, 10.1038/sj.onc.1210228

Matthaei, 2012, miRNA biomarkers in cyst fluid augment the diagnosis and management of pancreatic cysts, Clin Cancer Res, 18, 4713, 10.1158/1078-0432.CCR-12-0035

Sadakari, 2010, MicroRNA expression analyses in preoperative pancreatic juice samples of pancreatic ductal adenocarcinoma, JOP, 11, 587

Kanda, 2012, Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia, Gastroenterology, 142, 730, 10.1053/j.gastro.2011.12.042

Hong, 2012, Genome-wide CpG island profiling of intraductal papillary mucinous neoplasms of the pancreas, Clin Cancer Res, 18, 700, 10.1158/1078-0432.CCR-11-1718

de Planell-Saguer, 2010, Rapid in situ codetection of noncoding RNAs and proteins in cells and formalin-fixed paraffin-embedded tissue sections without protease treatment, Nat Protoc, 5, 1061, 10.1038/nprot.2010.62

Lu, 2009, Imaging individual microRNAs in single mammalian cells in situ, Nucleic Acids Res, 37, e100, 10.1093/nar/gkp482

Benjamini, 1995, Controlling the false discovery rate: a practical and powerful approach to multiple testing, J Royal Stat Soc Ser B Stat Methodol, 57, 289, 10.1111/j.2517-6161.1995.tb02031.x

Endo, 2013, MiR-1290 and its potential targets are associated with characteristics of estrogen receptor alpha-positive breast cancer, Endocr Relat Cancer, 20, 91, 10.1530/ERC-12-0207

Cowper-Sal lari, 2012, Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression, Nat Genet, 44, 1191, 10.1038/ng.2416

Song, 2010, Loss of FOXA1/2 is essential for the epithelial-to-mesenchymal transition in pancreatic cancer, Cancer Res, 70, 2115, 10.1158/0008-5472.CAN-09-2979

Liu, 2012, Serum microRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer, Clin Chem, 58, 610, 10.1373/clinchem.2011.172767

Ali, 2010, Differentially expressed miRNAs in the plasma may provide a molecular signature for aggressive pancreatic cancer, Am J Transl Res, 3, 28

Liu, 2012, Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer, Int J Cancer, 131, 683, 10.1002/ijc.26422

Labbaye, 2012, The emerging role of MIR-146A in the control of hematopoiesis, immune function and cancer, J Hematol Oncol, 5, 13, 10.1186/1756-8722-5-13

Mestdagh, 2008, High-throughput stem-loop RT-qPCR miRNA expression profiling using minute amounts of input RNA, Nucleic Acids Res, 36, e143, 10.1093/nar/gkn725

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Clinical Cancer Research

Tập 19 Số 13

3600-3610

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