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MicroRNA panel may help identify malignant pancreatic lesions
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A microRNA panel that assesses blood plasma levels may distinguish individuals with intraductal papillary mucinous neoplasms in the pancreas from healthy individuals, according to the results of a retrospective analysis.
Further, the test discriminated between patients with high-risk and low-risk intraductal papillary mucinous neoplasms (IPMN), according to the researchers.
“To be able to distinguish between these two sets of patients is important clinically,” study researcher Mokenge Malafa, MD, department chair and program leader of the gastrointestinal tumor program at Moffitt Cancer Center in Tampa, said in a press release. “It would help to personalize care such that high-risk IPMNs that warrant resection are properly identified while individuals with low-risk IPMNs are spared the substantial risks associated with unnecessary surgery.”
Because there are currently no accurate methods for the early diagnosis of pancreatic cancer, it is typically diagnosed at a late stage, according to study researcher Jennifer Permuth-Wey, PhD, assistant member in the departments of cancer epidemiology and gastrointestinal oncology at Moffitt Cancer Center.
Jennifer Permuth-Wey
Malafa, Permuth-Wey and colleagues sought to develop a noninvasive test to accurately detect precancerous lesions of the pancreas to aid in personalized risk assessment and care.
The researchers obtained preoperative plasma samples from 44 patients who underwent surgery to remove IPMNs, as well as 25 healthy individuals. They used the nCounter Human v2 miRNA Expression Assay Codeset (Nanostring Technologies) to measure the levels of 800 microRNAs from the plasma samples.
Determining a microRNA set that distinguishes patients with IPMNs from healthy individuals served as the primary study outcome. A secondary outcome included distinguishing patients with high-risk IPMNs — which included high-grade dysplasia and invasive carcinoma that should be surgically removed — from those with low-risk IPMNs, or low- and moderate-grade carcinoma.
The researchers identified a panel of 30 microRNAs that distinguished individuals with IPMNs (n = 42) from healthy individuals (n = 24), with an area under the curve (AUC) of 0.74 (95% CI, 62.3-86.5). The panel contained novel microRNAs as well as microRNAs previously implicated in pancreatic carcinogenesis that had two- to fourfold higher expression in patients than controls.
Further, the researchers developed a panel of five microRNAs that distinguished patients with high-risk, malignant IPMNs (n = 21) and low-risk, benign IPMNs (n = 21) with an AUC of 0.73 (0.73; 95% CI, 57.6-73.2).
Researchers then matched plasma and tissue samples from 12 IPMN cases and evaluated them for 160 microRNAs. Only three microRNA levels appeared positively correlated in plasma and tissue samples, which included miR-484, miR-330, miR-574 (P ˂ .05). These data showed that plasma and tissue samples from patients with IPMNs can have distinct microRNA expression profiles, according to the researchers.
The researchers acknowledged the study’s small sample size as a potential limitation to the findings. Further, they noted that the accuracy of both panels fell below the 90% accuracy threshold that many researchers believe may be necessary for clinical implication.
“Our study shows that new, relatively inexpensive digital technology could reliably measure [microRNAs] in blood plasma from individuals newly diagnosed with pancreatic cancer precursors and healthy individuals,” Permuth-Wey said in a press release. “This is promising news and could potentially lead to a noninvasive test for early detection of pancreatic cancer. However, the results are preliminary and much more research is needed to determine if a [microRNA-based] blood test could help diagnose pancreatic cancer earlier or more effectively than current methods.” – by Cameron Kelsall
Disclosure: Malafa, Permuth-Wey and one other study researcher report a patent pending related for the assay reported in this study. The other researchers report no relevant financial disclosures.
Perspective
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Philip Agop Philip, MD, PhD, FRCP
An unmet need is the accurate definition of pancreatic lesions by imaging and needle sampling to rule in/out major surgery. MicroRNAs are stable molecules that can be quantified in tissues and blood by several well-developed but non-standardized platforms. Their role in gene regulation is well studied in multiple diseases including pancreatic cancer. As such, microRNAs are an exciting category of molecules that can be of great potential in pancreatic cancer that has an empty list of biomarkers. It is therefore very timely to translate preclinical observations into patient management. The ultimate test would be in the context of prospective well-controlled clinical trials that have been long overdue.
Permuth-Wey and colleagues describe findings from a pilot study testing plasma microRNAs for diagnosing intraductal papillary mucinous neoplasms (IMPNs) and identifying those patients with significant risk for developing invasive cancer. Noninvasive microRNA profiling will prevent unnecessary morbid surgery in low-risk situations. This report is the first prospective study of microRNAs in the context of IMPNs. The authors identified a five microRNA signature that may represent clinically significant IPMN.
It is hoped that findings from this very small study would lead to well-designed prospective multi-institutional trials to confirm the findings and to further explore the clinical potential for microRNAs in pancreatic cancer. For example, microRNAs may provide an opportunity to interrogate a therapeutic target in real time. It is encouraging that altered expression levels of certain microRNAs were linked to critical genes such as NFkB and SMAD4. The lack of good correlation between the tissue and plasma microRNA expression was noteworthy and challenges our belief that cells and macromolecules that are shed from tumors faithfully represent the molecular status of the tumor cells. However, circulating microRNAs may reflect clinically more-relevant tumor/host biology and account for tumor heterogeneity. As we plan prospective studies, there is a need to develop well-established and biologically validated protocols for microRNA profiling in pancreatic cancer.
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