title: Candidate agents for pancreatic ductal adenocarcinoma identified by a sub-pathway based method.
abstract: OBJECTIVE
  Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death worldwide. This study aims to explore the molecular mechanism of PDAC and identify biologically active small molecules capable of targeting the sub-pathways which were dysregulated in the development of PDAC.
  
  
  METHODS
  The gene expression profile of GSE28735 microarray data (including 45 matching pairs of pancreatic tumor and adjacent non-tumor tissues) was downloaded from GEO (Gene Expression Omnibus) database. Differentially expressed genes (DEGs) between pancreatic tumor tissues and non-tumor tissues were identified, and then the sub-pathway enrichment analysis was performed. Moreover, an approach based on targeting sub-pathways was used to reveal potential agents for PDAC.
  
  
  RESULTS
  A total of 5315 DEGs were identified between pancreatic tumor tissues and non-tumor tissues with a false discovery rate of 0.01. Genes of collagen family and integrin receptor family which were involved in pathways of focal adhesion and ECM-receptor interaction respectively were differentially expressed in the pancreatic tumor tissue. Besides, a total of 85 small molecules including fludrocortisone, latamoxef and metronidazole were revealed by bioinformatics analysis.
  
  
  CONCLUSIONS
  This study proposed the use of an approach based on targeting sub-pathways to identify potential agents for PDAC. The sub-pathways and small molecules discovered in this study were not only related to PDAC but also play a role in perturbing the development of PDAC.
authors.affiliation: Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Lian-Jie
authors.initials: LJ
authors.lastname: Lin
authors.affiliation: Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Shao-Fu
authors.initials: SF
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang 110001, Liaoning Province, China. Electronic address: changqingzheng2@hotmail.com.
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Zheng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D058990:Molecular Targeted Therapy; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D000970:Antineoplastic Agents; D016023:Integrins; D003094:Collagen
keywords: Pancreatic ductal adenocarcinoma; Small molecules; Sub-pathway