title: Bioinformatic analyses revealed underlying biological functions correlated with oxaliplatin responsiveness.
abstract: Colorectal cancer is one of the most common cancers worldwide. Surgery is usually the primary treatment for colon cancers that have not spread to distant sites. However, chemotherapy may be considered after surgery to eliminate remaining cancer cells or in case the cancer has a high risk of recurrence. Oxaliplatin is often used in combination regimens such as FOLFOX, CapeOX, and FOLFOXIRI because of the cost-effectiveness of adjuvant treatment for patients and also the good tolerability profile. However, some patients show resistance to oxaliplatin which causes poor treatment outcomes. Most colon cancer studies focused on treatments and patient survival. Some studies focused on genetic associations of specific genes. However, pathway and network analyses of oxaliplatin resistance in colon cancer cells using gene expression patterns are still lacking. We performed a microarray analysis and found that endothelin-1 (EDN1), dishevelled segment polarity protein (DV1), toll-like receptor 5(TLR5), mitogen-activated protein kinase 3 (MAP2K3), phosphatidylinositol-4,5-bisphosphate 3-kinase, and catalytic subunit beta (PIK3CB) were closely related to responsiveness to oxaliplatin treatment. Furthermore, we found that the signal transduction, melanogenesis, and toll-like receptor signaling pathways might be involved in oxaliplatin-resistant colon cancer. These genes and pathways might be potential targets for improving oxaliplatin treatment in colon cancer patients.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Sukhontip
authors.initials: S
authors.lastname: Klahan
authors.affiliation: Department of Surgery, Cathay General Hospital, SiJhih, New Taipei City, Taiwan.|School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.|School of Medicine, Taipei Medical University, Taipei City, Taiwan.
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.|Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Chien
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Mei-Shin
authors.initials: MS
authors.lastname: Wu
authors.affiliation: Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Henry Sung-Ching
authors.initials: HS
authors.lastname: Wong
authors.affiliation: Division of General Surgery, Department of Surgery, Department of Neurosurgery Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan. wcc@tmu.edu.tw.|Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan. wcc@tmu.edu.tw.
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan. poliwei@tmu.edu.tw.|Division of General Surgery, Department of Surgery, Department of Neurosurgery Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan. poliwei@tmu.edu.tw.|Department of Surgery, College of Medicine, Taipei Medical University, Taipei, Taiwan. poliwei@tmu.edu.tw.|Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan. poliwei@tmu.edu.tw.|Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan. poliwei@tmu.edu.tw.|Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan. poliwei@tmu.edu.tw.
authors.forename: Po-Li
authors.initials: PL
authors.lastname: Wei
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008954:Models, Biological; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000627:therapeutic use; D000077150:Oxaliplatin; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin
keywords: Bioinformatic analysis; Colon cancer; Network and pathway analysis; Oxaliplatin