title: Up-regulation of AKAP13 and MAGT1 on cytoplasmic membrane in progressive hepatocellular carcinoma: a novel target for prognosis.
abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers and is associated with high mortality worldwide. The current gold standards for HCC surveillance are detection of serum α-fetoprotein (AFP) and ultrasonography; however, non-specificity of AFP and ultrasonography has frequently been reported. Therefore, alternative tools, especially novel specific tumor markers, are required. In this study, cytoplasmic membrane proteins were isolated from phorbol 12-myristate 13-acetate (PMA)-induced invasive HepG2 cells and identified using nano-scale liquid chromatographic tandem mass spectrometry (NLC-MS/MS) with comparison to non-treated controls. The results showed that two proteins, magnesium transporter protein 1 (MAGT1) and A-kinase anchor protein 13 (AKAP13), were highly expressed in PMA-treated HepG2 cells. This up-regulation was confirmed by real-time RT-PCR, western blot analysis, and immunofluorescent staining studies. Furthermore, evaluation of MAGT1 and AKAP13 expression in clinical HCC tissues by immunohistochemistry suggested that both proteins were strongly expressed in tumor tissues with significantly higher average immunoreactive scores of Remmele and Stegner (IRS) than in non-tumor tissues (P ≤ 0.005). In conclusion, the expression levels of MAGT1 and AKAP13 in HCC may be potential biomarkers for the diagnosis and prognosis of this cancer.
authors.affiliation: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University Bangkok 10400, Thailand.
authors.forename: Patamaporn
authors.initials: P
authors.lastname: Molee
authors.affiliation: Department of Helminthology, Faculty of Tropical Medicine, Mahidol University Bangkok 10400, Thailand.
authors.forename: Poom
authors.initials: P
authors.lastname: Adisakwattana
authors.affiliation: Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University Bangkok 10400, Thailand.
authors.forename: Onrapak
authors.initials: O
authors.lastname: Reamtong
authors.affiliation: Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University Bangkok 10400, Thailand.
authors.forename: Songsak
authors.initials: S
authors.lastname: Petmitr
authors.affiliation: Pathology Unit, Chulabhorn Hospital Bangkok 10210, Thailand.
authors.forename: Thaniya
authors.initials: T
authors.lastname: Sricharunrat
authors.affiliation: Department of Helminthology, Faculty of Tropical Medicine, Mahidol University Bangkok 10400, Thailand.
authors.forename: Nantana
authors.initials: N
authors.lastname: Suwandittakul
authors.affiliation: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University Bangkok 10400, Thailand.
authors.forename: Urai
authors.initials: U
authors.lastname: Chaisri
mesh_terms: D054758:A Kinase Anchor Proteins / Q000096:biosynthesis*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D027682:Cation Transport Proteins / Q000096:biosynthesis*; D002462:Cell Membrane / Q000378:metabolism; D002853:Chromatography, Liquid; D005260:Female; D005455:Fluorescent Antibody Technique; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation
chemical_list: D054758:A Kinase Anchor Proteins; C085467:AKAP13 protein, human; D014408:Biomarkers, Tumor; D027682:Cation Transport Proteins; C509698:MagT1 protein, human; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D011518:Proto-Oncogene Proteins
keywords: AKAP13; Hepatocellular carcinoma; MAGT1; cytoplasmic membrane proteins; immunohistochemistry; proteomics