Gene Signature Could Predict Development of Pancreatic Cancer, Allow Personalized Treatment

A deadly disease, primarily due to its late-stage detection, pancreatic cancer has the highest mortality rate of all major cancers: 94% of patients die within 5 years of diagnosis and nearly 75% die within the first year after being diagnosed. Treatment options are restrictive, with surgery possible in less than 20% of patients, and chemotherapy with or without radiation is then administered.

Now, scientists at the Moffitt Cancer Center have identified a microRNA gene signature that can recognize patients with premalignant pancreatic lesions (intraductal papillary neoplasms or IPMNs).

IPMNs are known to develop into pancreatic ductal adenocarcinomas, and earlier detection, the scientists predict, could have a significant impact on survival rates. According to study author Jennifer Permuth-Wey, PhD, MS, “IPMNs are established precursor lesions to pancreatic cancer that account for approximately half of all asymptomatic pancreatic cysts incidentally detected by computerized tomography scans or magnetic resonance imaging in the US each year,” and identifying and treating these premalignant lesions could reduce the number of people affected by the disease, she thinks.

For the study published in Cancer Prevention Research, the authors analyzed perioperative plasma collected from individuals confirmed to have developed IPMNs and compared them with samples from healthy controls. The research was based on the hypothesis that the microRNAs that were being evaluated are shed from IPMN tissues and can be detected in blood. Comparing the expression of 800 microRNAs between 42 IPMN samples and 24 controls, the researchers narrowed down a 30-microRNA signature (area underneath the curve (AUC) = 74.4; 95% confidence interval (CI), 62.3-86.5, P = .002), which included previously identified as well as some new microRNAs. These microRNAs had significantly greater expression in the IPMN samples. Additionally, a 5-microRNA signature was identified that could discriminate between 21 malignant and 21 benign IPMNs (AUC = 73.2; 95% CI, 57.6-88.9, P = .005).

This study is an extremely important step toward earlier detection of a disease with such dismal prognosis. Once validated in a broader population, the microRNA signature can be used to develop a blood test for adoption into routine clinical practice and would allow for a much earlier intervention than is currently possible.

Said Permuth-Wey, “The hope is that in the not-so-distant future a miRNA-based blood test can be used in conjunction with imaging features and other factors to aid the medical team in accurately predicting disease severity of IPMNs and other pancreatic cysts at the time of diagnosis or follow-up so that more informed personalized medical management decisions can be made.”