title: RNA sequencing-based analysis of gallbladder cancer reveals the importance of the liver X receptor and lipid metabolism in gallbladder cancer.
abstract: Gallbladder cancer (GBC) is an aggressive malignancy. Although surgical resection may be curable, most patients are diagnosed at an advanced unresectable disease stage. Cholelithiasis is the major risk factor; however the pathogenesis of the disease, from gallstone cholecystitis to cancer, is still not understood. To understand the molecular genetic underpinnings of this cancer and explore novel therapeutic targets for GBC, we examined the key genes and pathways involved in GBC using RNA sequencing. We performed gene expression analysis of 32 cases of surgically-resected GBC along with normal gallbladder tissue controls. We observed that 519 genes were differentially expressed between GBC and normal GB mucosal controls. The liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor (FXR) /RXR pathways were the top canonical pathways involved in GBC. Key genes in these pathways, including SERPINB3 and KLK1, were overexpressed in GBC, especially in female GBC patients. Additionally, ApoA1 gene expression suppressed in GBC as compared with normal control tissues. LXR and FXR genes, known to be important in lipid metabolism also function as tumor suppressors and their down regulation appears to be critical for GBC pathogenesis. LXR agonists may have therapeutic value and as potential therapeutic targets.
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Mingxin
authors.initials: M
authors.lastname: Zuo
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Apurva
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Donghui
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Surgical Gastroenterology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, UP, India.
authors.forename: Anu
authors.initials: A
authors.lastname: Behari
authors.affiliation: Department of Surgical Gastroenterology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, UP, India.
authors.forename: Vinay Kumar
authors.initials: VK
authors.lastname: Kapoor
authors.affiliation: Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Koay
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Chang
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jean-Nicholas
authors.initials: JN
authors.lastname: Vauthey
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Li
authors.affiliation: SciLifeLab, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Stockholm, Sweden.
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Espinoza
authors.affiliation: Department of Pathology, Advanced Center for Chronic Diseases (ACCDiS), UC-Center for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Roa
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Milind
authors.initials: M
authors.lastname: Javle
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005706:Gallbladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D000071518:Liver X Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000071518:Liver X Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated
keywords: RNA sequence; gallbladder cancer; lipid metabolism pathways; liver X receptor