Abstract
It is currently difficult for pathologists to diagnose pancreatic cancer (PC) using biopsy specimens because samples may have been from an incorrect site or contain an insufficient amount of tissue. Thus, there is a need to develop a platform-independent molecular classifier that accurately distinguishes benign pancreatic lesions from PC. Here, we developed a robust qualitative messenger RNA signature based on within-sample relative expression orderings (REOs) of genes to discriminate both PC tissues and cancer-adjacent normal tissues from non-PC pancreatitis and healthy pancreatic tissues. A signature comprising 12 gene pairs and 17 genes was built in the training datasets and validated in microarray and RNA-sequencing datasets from biopsy samples and surgically resected samples. Analysis of 1,007 PC tissues and 257 non-tumor samples from nine databases indicated that the geometric mean of sensitivity and specificity was 96.7%, and the area under receiver operating characteristic curve was 0.978 (95% confidence interval, 0.947–0.994). For 20 specimens obtained from endoscopic biopsy, the signature had a diagnostic accuracy of 100%. The REO-based signature described here can aid in the molecular diagnosis of PC and may facilitate objective differentiation between benign and malignant pancreatic lesions.
Highlights
Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in the United States and the sixth leading cause in China
We sorted the 20 reversal gene pair” (RGP) into descending order based on the rank difference (Rij) between PC and non-tumor tissues in the merged data from the training set and utilized the top−ranked k gene pairs for sample classification using majority vote rule
We developed and validated a qualitative relative expression orderings (REOs)-based signature consisting of 12 different gene pairs with 17 genes for the early and accurate molecular diagnosis of PC
Summary
Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in the United States and the sixth leading cause in China. Patients with PC have a 5-year survival rate of 8.5% in the United States and 7.2% in China (Siegel et al, 2019; Zhao et al, 2019). The diagnosis and treatment of pancreatic cancer remain challenging. Serum cancer antigen 199 (CA 19-9) is the only marker approved by the United States Food and Drug Administration for use in the routine management of PC. Imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS), and endoscopic
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