MedicalResearch.com Interview with: Jenny Permuth Wey, PhD, MS Assistant Member Departments of Cancer Epidemiology and Gastrointestinal Oncology Moffitt Cancer Center   Medical Research: What is the background for this study? What are the main findings? Dr. Wey: Pancreatic cancer is one of the deadliest cancers world-wide. It is currently the fourth leading cause of cancer-related deaths in the United States, and is predicted to become the second leading cause by 2030. Currently there are no accurate methods to diagnose pancreatic cancer early when a patient may be eligible for surgery to remove the tumor and hopefully survive longer. To beat this disease, early detection is key, and our team has dedicated efforts to studying pancreatic cancer in its ‘precancerous’ state because we and other researchers believe that the identification and treatment of precancerous pancreatic lesions offers a promising strategy to reduce the number of people losing their lives to this disease. Similar to how colon polyps can progress into colon cancer, we now know that certain types of pancreatic cystic lesions can progress into pancreatic cancer. Pancreatic cancer precursors/pre-cancers known as intraductal papillary mucinous neoplasms (IPMNs) account for nearly one-half of the estimated 150,000 asymptomatic pancreatic cysts detected as ‘incidental findings’ on computed tomography (CT) scans or magnetic resonance imaging (MRI) scans each year during the clinical work-up for an unrelated condition.  Imaging alone cannot reliably distinguish between benign, pre-cancerous, and cancerous cysts, and cannot differentiate ‘low-risk’intraductal papillary mucinous neoplasms' (defined as low- or moderate-grade disease) that can be monitored from ‘high-risk’ IPMNs (defined as high-grade or invasive disease) that should be surgically removed.  The decision to undergo pancreatic surgery is not trivial for the patient and medical team since pancreatic surgery can be associated with an estimated 40% chance of complications and a 4% chance of death. Noninvasive tests are needed to accurately detect precancerous lesions of the pancreas so that personalized risk assessment and care can be provided. microRNAs (miRNAs) are small molecules that act as ‘master-regulators’ of cancer-related processes in the body. One of the main purposes of our ‘proof of principle’ study was to measure miRNAs in the blood and determine whether a set of miRNAs could distinguish patients with IPMNs from healthy individuals. We then sought to determine whether a set of miRNAs could distinguish patients known to have ‘low-risk’ IPMNs from those with ‘high-risk’ IPMNs.  We show that new, relatively inexpensive digital technology could reliably measure miRNAs in blood plasma (the pale yellow liquid component of blood) from individuals newly-diagnosed with pancreatic cancer precursors (IPMNs) and healthy individuals.  Thirty miRNAs out of 800 tested showed higher levels in IPMN patients compared to healthy individuals, providing a preliminary ‘miRNA signature’ that may be found only in people with early pancreatic disease, suggesting it could serve as an early diagnostic tool.  Furthermore, we also provide preliminary data to suggest that a 5-miRNA signature can partially distinguish high-risk IPMNs that warrant resection from low-risk IPMNs that can be watched.  This is important clinically because it would be opportune 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 of mortality and morbidity associated with overtreatment from unnecessary surgery. (more…)

MedicalResearch.com Interview with: Tatjana Crnogorac-Jurcevic MD PhD Reader Centre for Molecular Oncology Barts Cancer Institute, Queen Mary University of London London UK  Medical Research: What is the background for this study? What are the main findings? Dr. Crnogorac-Jurcevic: Pancreatic adenocarcinoma (PDAC) is one of the most difficult cancers to detect. More than 80% of patients usually present at a late stage, with either locally advanced or with already metastatic disease. This is one of the major reasons for a bleak prognosis of this malignancy, which is typically 3-6 months and with <5% five-year survival. However, if patients are diagnosed with stage II disease, the survival rate is 20%, and at stage I, in patients with very small tumours, the five-year survival can increase up to 60%. In order to find biomarkers for early detection of this disease, we have performed in depth GeLC/MS/MS (SDS-PAGE-liquid chromatography-tandem mass spectrometry) analysis of 18 proteomes of urine samples collected from healthy controls, chronic pancreatitis, and patients with Pancreatic adenocarcinoma and obtained around 1500 non-redundant proteins. From these, three proteins, LYVE-1, REG1A, and TFF1, were selected for further analysis based on their known biological functions and statistical difference in comparisons of the experimental groups. These biomarkers were subsequently validated using ELISA assays in a multicenter cohort of urine samples: 87 from healthy people, 92 from patients with chronic pancreatitis, and 192 from PDAC patients. Multiple logistic regression was then applied: when comparing Pancreatic adenocarcinoma with healthy urine specimens, the resulting areas under the receiver-operating characteristic curves (AUC) of the three biomarkers combined into a panel were 0.89 (95% confidence interval: 0.84–0.94) in the training dataset (70% of the data) and 0.92 (95% confidence interval: 0.86–0.98) in the validation dataset (30% of the data). When the results from the analysis of PDAC stage I–II (n=71) urine samples were compared with the healthy urine specimens, the panel achieved AUCs of 0.90 (95% confidence interval: 0.84–0.96) and 0.93 (95% confidence interval: 0.84–1.00) in the training and validation datasets, respectively. In comparison to matching plasma CA19.9 values, the only Pancreatic adenocarcinoma biomarker in widespread clinical use (albeit mostly for monitoring of the disease), the panel achieved a higher AUC of 0.97 (95% confidence interval: 0.94–0.99) than CA19.9 (AUC 1/4 0.88; 95% confidence interval: 0.81–0.95, P=0.005). When combined with CA19.9, increased AUC of 0.99 (95% confidence interval: 0.97–1.00, P=0.04) was achieved, but this was not seen in a panel combined with plasma CA19.9 in stage I–IIA PDAC (n =17) vs. healthy sample comparison. (more…)