Micro-RNA Analysis of Pancreatic Cyst Fluid for Diagnosing Malignant Transformation of Intraductal Papillary Mucinous Neoplasm by Comparing Intraductal Papillary Mucinous Adenoma and Carcinoma

Shirakami, Yohei; Iwashita, Takuji; Uemura, Shiro; Imai, Hisashi; Murase, Katsutoshi; Shimizu, Masahito

doi:10.3390/jcm10112249

Cited by 13 publications

(10 citation statements)

References 26 publications

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“…The reported sensitivity was 10.0%, the specificity 100.0%, the positive predicted value 100.0%, the negative predicted value 85.2%, and the overall diagnostic accuracy was 85.5%. Similarly, Shirakami Y. et al described a panel of six miRNA enriched in IPMN with invasive carcinoma when compared with benign IPMN [ 83 ].…”

Section: New Perspectivesmentioning

confidence: 99%

Humoral Predictors of Malignancy in IPMN: A Review of the Literature

Nista

Schepis

Candelli

et al. 2021

IJMS

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Pancreatic cystic lesions are increasingly detected in cross-sectional imaging. Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing subtype of the pancreatic cyst lesions arising from the pancreatic duct system. IPMN is a potential precursor of pancreatic cancer. The transformation of IPMN in pancreatic cancer is progressive and requires the occurrence of low-grade dysplasia, high-grade dysplasia, and ultimately invasive cancer. Jaundice, enhancing mural nodule >5 mm, main pancreatic duct diameter >10 mm, and positive cytology for high-grade dysplasia are considered high-risk stigmata of malignancy. While increased levels of carbohydrate antigen 19-9 (CA 19-9) (>37 U/mL), main pancreatic duct diameter 5–9.9 mm, cyst diameter >40 mm, enhancing mural nodules <5 mm, IPMN-induced acute pancreatitis, new onset of diabetes, cyst grow-rate >5 mm/year are considered worrisome features of malignancy. However, cross-sectional imaging is often inadequate in the prediction of high-grade dysplasia and invasive cancer. Several studies evaluated the role of humoral and intra-cystic biomarkers in the prediction of malignancy in IPMN. Carcinoembryonic antigen (CEA), CA 19-9, intra-cystic CEA, intra-cystic glucose, and cystic fluid cytology are widely used in clinical practice to distinguish between mucinous and non-mucinous cysts and to predict the presence of invasive cancer. Other biomarkers such as cystic fluid DNA sequencing, microRNA (mi-RNA), circulating microvesicles, and liquid biopsy are the new options for the mini-invasive diagnosis of degenerated IPMN. The aim of this study is to review the literature to assess the role of humoral and intracystic biomarkers in the prediction of advanced IPMN with high-grade dysplasia or invasive carcinoma.

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Section: New Perspectivesmentioning

confidence: 99%

Humoral Predictors of Malignancy in IPMN: A Review of the Literature

Nista

Schepis

Candelli

et al. 2021

IJMS

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“…Approximately 80% of IPMNs show high expression for microRNAs-miR-155 and miR-21. The expression of these microRNAs is particularly noticeable in advanced IPMNs and has been investigated as a potential diagnostic approach in pancreatic cyst fluid as a marker for evaluating the malignant transformation of IPMNs (Shirakami et al, 2021).…”

Section: Genetic Alterationsmentioning

confidence: 99%

Updates in the Diagnosis of Intraductal Neoplasms of the Pancreas

2022

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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer worldwide. There are many reasons for this dismal prognosis, including the advanced stage at the time of diagnosis and the lack of effective therapeutic approaches. Intraductal papillary mucinous neoplasms (IPMNs) represent detectable and treatable precursor lesions of PDAC. Our understanding of the pathology of IPMNs has evolved over the past few decades, and new advances in diagnostic tools have emerged. The new World Health Organization (WHO) classification scheme now recognizes the previously considered variants of IPMNs, such as intraductal oncocytic papillary neoplasms (IOPNs) and intraductal tubulopapillary neoplasms (ITPNs), as distinct neoplasms. New imaging and molecular diagnostic tests are being developed to recognize these PDAC precursor lesions better. Here, we review the advances in diagnostic tools for IPMNs, IOPNs, and ITPNs, emphasizing the new (5th edition, 2019) WHO classification for pathological diagnosis, molecular markers, new laboratory tests, and imaging tools.

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“…In a further study, six miRNAs were detected at significantly higher levels in cyst fluid from IPMC than in cyst fluid from IPMA. They included miR-711, miR-3679-5p, miR-6126, miR-6780b-5p, miR-6798-5p, and miR-6879-5p, differing notably from the above group, perhaps due to the small sample size [ 64 ]. Wang et al identified miRNAs that have decreased malignant cyst fluid contents compared with benign cysts (miR-451a and miR-4284) [ 65 ].…”

Section: Microrna Expression In Patients With Cystic Pancreatic Lesio...mentioning

confidence: 99%

MicroRNAs as Indicators of Malignancy in Pancreatic Ductal Adenocarcinoma (PDAC) and Cystic Pancreatic Lesions

Prinz

Fehring

Frese

2022

Cells

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The dysregulation of microRNAs has recently been associated with cancer development and progression in pancreatic ductal adenocarcinoma (PDAC) and cystic pancreatic lesions. In solid pancreatic tumor tissue, the dysregulation of miR-146, miR-196a/b, miR-198, miR-217, miR-409, and miR-490, as well as miR-1290 has been investigated in tumor biopsies of patients with PDAC and was reported to predict cancer presence. However, the value of the predictive biomarkers may further be increased during clinical conditions suggesting cancer development such as hyperinsulinemia or onset of diabetes. In this specific context, the dysregulation of miR-486 and miR-196 in tumors has been observed in the tumor tissue of PDAC patients with newly diagnosed diabetes mellitus. Moreover, miR-1256 is dysregulated in pancreatic cancer, possibly due to the interaction with long non-coding RNA molecules that seem to affect cell-cycle control and diabetes manifestation in PDAC patients, and, thus, these three markers may be of special or “sentinel value”. In blood samples, Next-generation sequencing (NGS) has also identified a set of microRNAs (miR-20a, miR-31-5p, miR-24, miR-25, miR-99a, miR-185, and miR-191) that seem to differentiate patients with pancreatic cancer remarkably from healthy controls, but limited data exist in this context regarding the prediction of cancer presences and outcomes. In contrast to solid pancreatic tumors, in cystic pancreatic cancer lesions, as well as premalignant lesions (such as intraductal papillary neoplasia (IPMN) or mucinous-cystic adenomatous cysts (MCAC)), the dysregulation of a completely different expression panel of miR-31-5p, miR-483-5p, miR-99a-5p, and miR-375 has been found to be of high clinical value in differentiating benign from malignant lesions. Interestingly, signal transduction pathways associated with miR-dysregulation seem to be entirely different in patients with pancreatic cysts when compared to PDAC. Overall, the determination of these different dysregulation “panels” in solid tumors, pancreatic cysts, obtained via fine-needle aspirate biopsies and/or in blood samples at the onset or during the treatment of pancreatic diseases, seems to be a reasonable candidate approach for predicting cancer presence, cancer development, and even therapy responses.

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Micro-RNA Analysis of Pancreatic Cyst Fluid for Diagnosing Malignant Transformation of Intraductal Papillary Mucinous Neoplasm by Comparing Intraductal Papillary Mucinous Adenoma and Carcinoma

Cited by 13 publications

References 26 publications

Humoral Predictors of Malignancy in IPMN: A Review of the Literature

Humoral Predictors of Malignancy in IPMN: A Review of the Literature

Updates in the Diagnosis of Intraductal Neoplasms of the Pancreas

MicroRNAs as Indicators of Malignancy in Pancreatic Ductal Adenocarcinoma (PDAC) and Cystic Pancreatic Lesions

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