MicroRNA miR-155 is a biomarker of early pancreatic neoplasia

Habbe, Nils; Koorstra, Jan Bart M.; Mendell, Joshua T.; Offerhaus, G. Johan A.; Ryu, Ji Kon; Feldmann, Georg; Mullendore, Michael E.; Goggins, Michael; Hong, Seung Mo; Maitra, Anirban

doi:10.4161/cbt.8.4.7338

Cited by 269 publications

(152 citation statements)

References 49 publications

(68 reference statements)

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“…Aberrant miRNA expression is widespread in human cancers, including pancreatic adenocarcinomas, as we and others have demonstrated [25,26,27,28]. Recent studies from our group [29,30], and others [31], have also established aberrant miRNA expression in precursor lesions of pancreatic cancer, reinforcing the notion that abnormal miRNA expression can be observed early during multistep carcinogenesis. In addition, cancer-associated miRNAs, which are shed by neoplastic cells, are readily detectable in the peripheral circulation of patients [32], and are emerging as candidate biomarkers for the early detection of cancer [33,34,35].…”

Section: Introductionsupporting

confidence: 48%

“…Aberrations of miRNA expression are widespread across human cancers [25,26,27,28], and as Lu et al [51] have reported, noncoding RNA profiles can reliably classify cancer subtypes, including outperforming global coding gene expression as classifiers. We and several groups have reported recurrent miRNA alterations in pancreatic cancer, and our group was one of the first to report comparable abnormalities in noninvasive precursor lesions of ductal adenocarcinomas [29,30]. Thus, Habbe et al [29] assessed the relative expression levels of a panel of twelve miRNAs known to be upregulated in pancreatic cancer in 15 noninvasive IPMNs, and found miR-21 (mean 12.1-fold) and miR-155 (mean 11.6-fold) to be differentially expressed, when compared to normal pancreas.…”

Section: Discussionmentioning

confidence: 99%

“…We and several groups have reported recurrent miRNA alterations in pancreatic cancer, and our group was one of the first to report comparable abnormalities in noninvasive precursor lesions of ductal adenocarcinomas [29,30]. Thus, Habbe et al [29] assessed the relative expression levels of a panel of twelve miRNAs known to be upregulated in pancreatic cancer in 15 noninvasive IPMNs, and found miR-21 (mean 12.1-fold) and miR-155 (mean 11.6-fold) to be differentially expressed, when compared to normal pancreas. These promising findings in IPMN tissues encouraged us to focus on miRNA expression in cyst fluid samples.…”

Section: Discussionmentioning

confidence: 99%

“…In light of the very few samples with associated invasive cancer (n = 3), we did not attempt to determine if miR-21, or other miRNAs, can further differentiate invasive from noninvasive lesions within the subset of mucinous precursor cysts, and this rather important question will be addressed in future cyst fluid studies. Nonetheless, the emergence of miR-21 as the most promising biomarker candidate in cyst fluid is not surprising, given its preeminent role as one of the original ‘onco-miRs’ in human neoplasia [54], and its well-documented overexpression in noninvasive precursor lesions of pancreatic cancer [29,30]. …”

Section: Discussionmentioning

confidence: 99%

“…Quantitative reverse transcription PCR (qRT-PCR) for miRNAs was performed using pre-designed TaqMan® miRNA assays (Applied Biosystems, Foster City, Calif., USA) with the 7300 Real-Time PCR system (Applied Biosystems). The assays are two-step protocol, including reverse transcription with human mature miRNA-specific RT primers, followed by real-time PCR with miRNA specific primers, as previously described [29,30]. These assays target only the mature miRNA sequence and the precursors are not detected.…”

Section: Methodsmentioning

confidence: 99%

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Elevated microRNA miR-21 Levels in Pancreatic Cyst Fluid Are Predictive of Mucinous Precursor Lesions of Ductal Adenocarcinoma

et al. 2011

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Background: Biomarkers for the diagnostic classification of pancreatic cysts are urgently needed. Deregulated microRNA (miRNAs) expression is widespread in pancreatic cancer. We assessed whether aberrant miRNAs in pancreatic cyst fluid could be used as potential biomarkers for cystic precursor lesions of pancreatic cancer. Methods: Cyst fluid specimens were prospectively collected from 40 surgically resected pancreatic cysts, and small RNAs were extracted. The ‘mucinous’ cohort included 14 intraductal papillary mucinous neoplasms (including 3 with an associated adenocarcinoma) and 10 mucinous cystic neoplasms; the ‘nonmucinous’ cohort included 11 serous cystadenomas and 5 other benign cysts. Quantitative reverse transcription PCR was performed for five miRNAs (miR-21, miR-155, miR-221, miR-17-3p, miR-191), which were previously reported as overexpressed in pancreatic adenocarcinomas. Results: Significantly higher expression of miR-21, miR-221, and miR-17-3p was observed in the mucinous versus nonmucinous cysts (p < 0.01), with the mean relative fold differences being 7.0-, 7.9-, and 5.4-fold, respectively. Receiver operating characteristic curves demonstrated the highest median area under the curve for miR-21, with a median specificity of 76%, at a sensitivity of 80%. Conclusion: This pilot study demonstrates that profiling miRNAs in pancreatic cyst fluid samples is feasible and can yield potential biomarkers for the classification of cystic lesions of the pancreas.

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Section: Introductionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Elevated microRNA miR-21 Levels in Pancreatic Cyst Fluid Are Predictive of Mucinous Precursor Lesions of Ductal Adenocarcinoma

et al. 2011

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The “Malignant Truth” About the Recurrence of Pancreatic Intraductal Papillary Mucinous Neoplasms

Frampton¹,

Pai²,

Krell³

et al. 2012

Arch Surg

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MicroRNA Signatures as Biomarkers in Cancer

Adams

Slack

2015

Encyclopedia of Life Sciences

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Microribonucleic acids (miRNAs) are a class of small noncoding RNAs that regulate gene expression posttranscriptionally and control many biological processes including tumourigenesis. Given that, miRNA levels are heavily dysregulated in tumour tissues, many of these RNAs have been identified as classifiers for particular cancer subtypes. In addition, miRNA gene signatures can provide prognostic value, are associated with tumourigenic processes such as metastasis and can identify certain tumour cell types including drug‐resistant and cancer stem cell populations. To gain a better molecular understanding of therapeutic response and disease relapse, there has been an impetus to develop miRNA biomarker profiles through less invasive strategies (i.e. from serum and other sources) rather than from repeated biopsy near the original tumour site. Through these techniques, miRNAs have been found to exist in cell‐free fractions, in exosomes and in circulating tumour cells. While it is still unclear about the mechanisms guiding the release of miRNAs into the serum and other sources, overall, miRNAs have the potential to be used in understanding the pathogenesis of disease prognosis and for diagnostic purposes and in the development of new therapeutic treatment regimens. Key Concepts MicroRNAs function as master regulators of gene expression at the posttranscriptional level. MicroRNAs can function as oncogenes or tumour suppressors in a cell‐context‐dependent manner. MicroRNAs are stable, found in serum and other biofluids and make good non‐invasive biomarkers. MicroRNA profiles are associated with therapeutic treatments and disease outcomes. MicroRNAs can themselves be therapeutic agents or therapeutic targets.

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MicroRNA miR-155 is a biomarker of early pancreatic neoplasia

Cited by 269 publications

References 49 publications

Elevated microRNA miR-21 Levels in Pancreatic Cyst Fluid Are Predictive of Mucinous Precursor Lesions of Ductal Adenocarcinoma

Elevated microRNA miR-21 Levels in Pancreatic Cyst Fluid Are Predictive of Mucinous Precursor Lesions of Ductal Adenocarcinoma

The “Malignant Truth” About the Recurrence of Pancreatic Intraductal Papillary Mucinous Neoplasms

MicroRNA Signatures as Biomarkers in Cancer

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