title: AMPKα modulation in cancer progression: multilayer integrative analysis of the whole transcriptome in Asian gastric cancer.
abstract: Gastric cancer is the most common cancer in Asia and most developing countries. Despite the use of multimodality therapeutics, it remains the second leading cause of cancer death in the world. To identify the molecular underpinnings of gastric cancer in the Asian population, we applied an RNA-sequencing approach to gastric tumor and noncancerous specimens, generating 680 million informative short reads to quantitatively characterize the entire transcriptome of gastric cancer (including mRNAs and miRNAs). A multilayer analysis was then developed to identify multiple types of transcriptional aberrations associated with different stages of gastric cancer, including differentially expressed mRNAs, recurrent somatic mutations, and key differentially expressed miRNAs. Through this approach, we identified the central metabolic regulator AMP-activated protein kinase (AMPK)α as a potential functional target in Asian gastric cancer. Furthermore, we experimentally showed the translational relevance of this gene as a potential therapeutic target for early-stage gastric cancer in Asian patients. Together, our findings not only provide a valuable information resource for identifying and elucidating the molecular mechanisms of Asian gastric cancer, but also represent a general integrative framework to develop more effective therapeutic targets.
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030,USA.
authors.forename: Yon Hui
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030,USA.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-749, Korea.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul 120-749, Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Cheong
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul 120-749, Korea.
authors.forename: Hoguen
authors.initials: H
authors.lastname: Kim
authors.affiliation: Partek Inc., St. Louis, MO 63141, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Partek Inc., St. Louis, MO 63141, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Downey
authors.affiliation: Life Technologies, Foster City, CA 94404, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Dyer
authors.affiliation: Life Technologies, Foster City, CA 94404, USA.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Life Technologies, Foster City, CA 94404, USA.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Sun
authors.affiliation: Life Technologies, Foster City, CA 94404, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Beasley
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-749, Korea.
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul 120-749, Korea.
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Noh
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Weinstein
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030,USA.
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030,USA.
authors.forename: Garth
authors.initials: G
authors.lastname: Powis
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs; D009154:Mutation; D012333:RNA, Messenger; D017421:Sequence Analysis; D013274:Stomach Neoplasms / Q000235:genetics*; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D055372:AMP-Activated Protein Kinases