Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that lacks effective biomarkers for early detection. We hypothesized that circulating long non-coding RNAs (lncRNAs) may act as diagnostic markers of incidentally-detected cystic PDAC precursors known as intraductal papillary mucinous neoplasms (IPMNs) and predictors of their pathology/histological classification. Using NanoString nCounter® technology, we measured the abundance of 28 candidate lncRNAs in pre-operative plasma from a cohort of pathologically-confirmed IPMN cases of various grades of severity and non-diseased controls. Results showed that two lncRNAs (GAS5 and SRA) aided in differentiating IPMNs from controls. An 8-lncRNA signature (including ADARB2-AS1, ANRIL, GLIS3-AS1, LINC00472, MEG3, PANDA, PVT1, and UCA1) had greater accuracy than standard clinical and radiologic features in distinguishing ‘aggressive/malignant’ IPMNs that warrant surgical removal from ‘indolent/benign’ IPMNs that can be observed. When the 8-lncRNA signature was combined with plasma miRNA data and quantitative ‘radiomic’ imaging features, the accuracy of predicting IPMN pathological classification improved. Our findings provide novel information on the ability to detect lncRNAs in plasma from patients with IPMNs and suggest that an lncRNA-based blood test may have utility as a diagnostic adjunct for identifying IPMNs and their pathology, especially when incorporated with biomarkers such as miRNAs, quantitative imaging features, and clinical data.
Highlights
® NanoString nCounter technology, we measured the abundance of 28 candidate lncRNAs in preoperative plasma from a cohort of pathologically-confirmed Intraductal papillary mucinous neoplasms (IPMNs) cases of various grades of severity and non-diseased controls
Studies reveal that the 5-year survival rate for patients with noninvasive IPMNs is greater than 70%, which is significantly higher than the 22–45% rate for individuals with resected invasive IPMNs and the 10–25% survival rate reported for individuals with resected conventional PDACs9
Pre-operative plasma samples were evaluated for 57 IPMN cases and 24 non-diseased controls frequency-matched by age-group and gender
Summary
® NanoString nCounter technology, we measured the abundance of 28 candidate lncRNAs in preoperative plasma from a cohort of pathologically-confirmed IPMN cases of various grades of severity and non-diseased controls. Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are a morphologically distinct set of tumors located in the duct epithelium and are characterized by papillary epithelial proliferation and mucin production, leading to cystic dilation of involved ducts[3] These cystic PDAC precursor lesions (‘precancers’) comprise almost half of the ~150,000 asymptomatic pancreatic cysts detected incidentally in the general population each year by computed tomography (CT) scans and magnetic resonance imaging (MRI)[4, 5]. Despite their radiologic detection, the only way to accurately examine their severity which ranges from noninvasive/pre-malignant (low-grade (LG), moderate-grade (MG), or high-grade (HG) dysplasia) to invasive carcinoma is through surgical resection, which carries significant risks of morbidity and mortality[6,7,8]. Given emerging data on the role of lncRNAs in PDAC initiation, progression, and outcomes[31,32,33,34,35,36,37,38,39] and evidence to support lncRNA detection in circulation[38, 40,41,42,43,44], we conducted the first study to measure the abundance of circulating lncRNAs from patients with IPMNs
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
