title: Identification of potential biomarkers to differentially diagnose solid pseudopapillary tumors and pancreatic malignancies via a gene regulatory network.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, 210023, China. lipengping2005@163.com.
authors.forename: Pengping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China. huyuebing2000@163.com.
authors.forename: Yuebing
authors.initials: Y
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, 210023, China. nju_yj@163.com.
authors.forename: Jiao
authors.initials: J
authors.lastname: Yi
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, 210023, China. jlee@nju.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, 210023, China. yangjie@nju.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, 210023, China. jwang@nju.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D003937:Diagnosis, Differential; D053263:Gene Regulatory Networks; D006801:Humans; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor