Abstract
The availability of robust classification algorithms for the identification of high risk individuals with resectable disease is critical to improving early detection strategies and ultimately increasing survival rates in PC. We leveraged high quality biospecimens with extensive clinical annotations from patients that received treatment at the Medstar-Georgetown University hospital. We used a high resolution mass spectrometry based global tissue profiling approach in conjunction with multivariate analysis for developing a classification algorithm that would predict early stage PC with high accuracy. The candidate biomarkers were annotated using tandem mass spectrometry. We delineated a six metabolite panel that could discriminate early stage PDAC from benign pancreatic disease with >95% accuracy of classification (Specificity = 0.85, Sensitivity = 0.9). Subsequently, we used multiple reaction monitoring mass spectrometry for evaluation of this panel in plasma samples obtained from the same patients. The pattern of expression of these metabolites in plasma was found to be discordant as compared to that in tissue. Taken together, our results show the value of using a metabolomics approach for developing highly predictive panels for classification of early stage PDAC. Future investigations will likely lead to the development of validated biomarker panels with potential for clinical translation in conjunction with CA-19-9 and/or other biomarkers.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) represents 90% of pancreatic neoplasms and the fourth leading cause of cancer death in the United States [1, 2].Due to the retroperitoneal location of the pancreas, these tumors are difficult to detect; progression of pancreatic cancer is often asymptomatic until late stages of the disease [3,4,5,6,7]
The clinical cohort used in this study consisted of a local population of patients with clinical presentation of benign (n = 15), precancerous lesions (PL) (n = 20) or early stage (IA, IB, IIA) PDAC (n = 19)
PLs exhibit a spectrum of clinical behaviors, this patient cohort was enriched for cystic pancreatic neoplasms with clinical, radiologic, and/or cytologic features associated with progression to invasive pancreatic cancer
Summary
Due to the retroperitoneal location of the pancreas, these tumors are difficult to detect; progression of pancreatic cancer is often asymptomatic until late stages of the disease [3,4,5,6,7]. Surgical resection offers the only opportunity for cure, since early diagnosis www.oncotarget.com is uncommon, only 20% of patients are candidates for surgery while the majority of patients present with advanced disease. The median survival for advanced or metastatic pancreatic cancer is less than 5% at 5 years [8]. The subsets of patients diagnosed with stage I disease or incidentally discovered PDAC have improved survival relative to symptomatic surgical patients [9]. Early detection is likely to improve outcomes
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