title: Integrative bioinformatic analyses of an oncogenomic profile reveal the biology of endometrial cancer and guide drug discovery.
abstract: A major challenge in personalized cancer medicine is to establish a systematic approach to translate huge oncogenomic datasets to clinical situations and facilitate drug discovery for cancers such as endometrial carcinoma. We performed a genome-wide somatic mutation-expression association study in a total of 219 endometrial cancer patients from TCGA database, by evaluating the correlation between ~5,800 somatic mutations to ~13,500 gene expression levels (in total, ~78, 500, 000 pairs). A bioinformatics pipeline was devised to identify expression-associated single nucleotide variations (eSNVs) which are crucial for endometrial cancer progression and patient prognoses. We further prioritized 394 biologically risky mutational candidates which mapped to 275 gene loci and demonstrated that these genes collaborated with expression features were significantly enriched in targets of drugs approved for solid tumors, suggesting the plausibility of drug repurposing. Taken together, we integrated a fundamental endometrial cancer genomic profile into clinical circumstances, further shedding light for clinical implementation of genomic-based therapies and guidance for drug discovery.
authors.affiliation: Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.|Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Henry Sung-Ching
authors.initials: HS
authors.lastname: Wong
authors.affiliation: Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.|Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yung-Shun
authors.initials: YS
authors.lastname: Juan
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: HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.|The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.|Academia Sinica, Taipei, Taiwan.|Department of Obstetrics and Gynecology, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Hsu
authors.affiliation: Academia Sinica, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Huang-Hui
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Academia Sinica, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Liu
authors.affiliation: Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.|Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, Taiwan.|Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D016208:Databases, Factual; D055808:Drug Discovery / Q000379:methods*; D058492:Drug Repositioning; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D023281:Genomics / Q000379:methods*; D006801:Humans; D009154:Mutation / Q000235:genetics; D057285:Precision Medicine
chemical_list: D014408:Biomarkers, Tumor
keywords: cancer drivers; cancer drug repurposing; cancer genomics; endometrial cancers; expression-associated somatic mutations