title: Identification of prosaposin and transgelin as potential biomarkers for gallbladder cancer using quantitative proteomics.
abstract: Gallbladder cancer is an uncommon but lethal malignancy with particularly high incidence in Chile, India, Japan and China. There is a paucity of unbiased large-scale studies investigating molecular basis of gallbladder cancer. To systematically identify differentially regulated proteins in gallbladder cancer, iTRAQ-based quantitative proteomics of gallbladder cancer was carried out using Fourier transform high resolution mass spectrometry. Of the 2575 proteins identified, proteins upregulated in gallbladder cancer included several lysosomal proteins such as prosaposin, cathepsin Z and cathepsin H. Downregulated proteins included serine protease HTRA1 and transgelin, which have been reported to be downregulated in several other cancers. Novel biomarker candidates including prosaposin and transgelin were validated to be upregulated and downregulated, respectively, in gallbladder cancer using tissue microarrays. Our study provides the first large scale proteomic characterization of gallbladder cancer which will serve as a resource for future discovery of biomarkers for gallbladder cancer.
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
authors.forename: Nandini A
authors.initials: NA
authors.lastname: Sahasrabuddhe
authors.affiliation: Centre for Genomics, Molecular and Human Genetics, Jiwaji University, Gwalior 474011, India; School of Studies in Zoology, Jiwaji University, Gwalior, India.
authors.forename: Mustafa A
authors.initials: MA
authors.lastname: Barbhuiya
authors.affiliation: Centre for Genomics, Molecular and Human Genetics, Jiwaji University, Gwalior 474011, India.
authors.forename: Shushruta
authors.initials: S
authors.lastname: Bhunia
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Amrita School of Biotechnology, Amrita University, Kollam, India.
authors.forename: Tejaswini
authors.initials: T
authors.lastname: Subbannayya
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
authors.forename: Harsha
authors.initials: H
authors.lastname: Gowda
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
authors.forename: Jayshree
authors.initials: J
authors.lastname: Advani
authors.affiliation: Cancer Hospital and Research Institute, Gwalior, India.
authors.forename: Braj R
authors.initials: BR
authors.lastname: Shrivastav
authors.affiliation: LAB SURGPATH, Mumbai, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Navani
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pathology, Universidad de La Frontera, CEGIN-BIOREN, Temuco, Chile.
authors.forename: Pamela
authors.initials: P
authors.lastname: Leal
authors.affiliation: Department of Pathology, Pontificia Universidad Catolica de Chile, Santiago, Chile.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Roa
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Raghothama
authors.initials: R
authors.lastname: Chaerkady
authors.affiliation: Cancer Hospital and Research Institute, Gwalior, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Chatterjee
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Centre for Genomics, Molecular and Human Genetics, Jiwaji University, Gwalior 474011, India; School of Studies in Zoology, Jiwaji University, Gwalior, India. Electronic address: pk_tiwari@hotmail.com.
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Tiwari
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002853:Chromatography, Liquid; D005704:Gallbladder / Q000378:metabolism / Q000473:pathology*; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000032:analysis* / Q000235:genetics; D009124:Muscle Proteins / Q000032:analysis* / Q000235:genetics; D020543:Proteome / Q000032:analysis / Q000235:genetics; D040901:Proteomics; D049231:Saposins / Q000032:analysis* / Q000235:genetics; D053719:Tandem Mass Spectrometry; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D008840:Microfilament Proteins; D009124:Muscle Proteins; C483345:PSAP protein, human; D020543:Proteome; D049231:Saposins; C051615:transgelin
keywords: Biomarkers; Gallbladder cancer; Prosaposin; Quantitative proteomics; Transgelin; iTRAQ