Identification of potential biomarkers to differentially diagnose solid pseudopapillary tumors and pancreatic malignancies via a gene regulatory network

Pengping Li, Yuebing Hu, Jiao Yi, Jie Li, Jie Yang, Jin Wang

Solid pseudopapillary neoplasms (SPN) are pancreatic tumors with low malignant potential and good prognosis. However, differential diagnosis between SPN and pancreatic malignancies including pancreatic neuroendocrine tumor (PanNET) and ductal adenocarcinoma (PDAC) is difficult. This study tried to identify candidate biomarkers for the distinction between SPN and the two malignant pancreatic tumors by examining the gene regulatory network of SPN. The gene regulatory network for SPN was constructed by a co-expression model. Genes that have been reported to be correlated with SPN were used as the clues to hunt more SPN-related genes in the network according to a shortest path approach. By means of the K-nearest neighbor algorithm (KNN) classifier evaluated by the jackknife test, sets of genes to distinguish SPN and malignant pancreatic tumors were determined. We took a new strategy to identify candidate biomarkers for differentiating SPN from the two malignant pancreatic tumors PanNET and PDAC by analyzing shortest paths among SPN-related genes in the gene regulatory network. 43 new SPN-relevant genes were discovered, among which, we found hsa-miR-194 and hsa-miR-7 along with 7 transcription factors (TFs) such as SOX11, SMAD3 and SOX4 etc. could correctly differentiate SPN from PanNET, while hsa-miR-204 and 4 TFs such as SOX9, TCF7 and PPARD etc. were demonstrated as the potential markers for SPN versus PDAC. 14 genes were demonstrated to serve as the candidate biomarkers for distinguishing SPN from PanNET and PDAC when considering them as malignant pancreatic tumors together. This study provides new candidate genes related to SPN and the potential biomarkers to differentiate SPN from PanNET and PDAC, which may help to diagnose patients with SPN in clinical setting. Furthermore, candidate biomarkers such as SOX11 and hsa-miR-204 which could cause cell proliferation but inhibit invasion or metastasis may be of importance in understanding the molecular mechanism of pancreatic oncogenesis and could be possible therapeutic targets for malignant pancreatic tumors.