Biomarker development for pancreatic ductal adenocarcinoma using integrated analysis of mRNA and miRNA expression

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, which has dismal prognosis because of its silent early symptoms, high metastatic potential, and resistance to conventional therapies. Although a PDAC patient who is diagnosed at an early stage would have a substantial increase in chance of survival, the survival rate is poor because there is no efficient non-invasive diagnostic test in the early stage. In this study, we developed an efficient prediction models to detect PDAC in its early stages. Our prediction models use both mRNA and miRNA expression data from 104 PDAC tissues and 17 normal pancreatic tissues using microarray technology. After quality control, we built prediction models based on support vector machine (SVM) from mRNA and miRNA expressions for detecting early PDAC. To prevent over-fitting effect, we conducted leave-one-out cross validation (LOOCV) and 5-fold cross validation (CV). For independent validation of prediction models, we performed evaluation on independent datasets from Gene Expression Omnibus (GEO). After the validation, we identified 28 single markers and 231 combinations of markers with powerful prediction performance. In addition, the marker candidates are annotated with cancer pathways using gene ontology analysis. Our prediction models for PDAC may have potential for early diagnosis of PDAC.

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