title: Increased Expression of the Autocrine Motility Factor is Associated With Poor Prognosis in Patients With Clear Cell-Renal Cell Carcinoma.
abstract: Glucose-6-phosphate isomerase (GPI), also known as phosphoglucose isomerase, was initially identified as the second glycolytic enzyme that catalyzes the interconversion of glucose-6-phosphate to fructose-6-phosphate. Later studies demonstrated that GPI was the same as the autocrine motility factor (AMF), and that it mediates its biological effects through the interaction with its surface receptor (AMFR/gp78). In this study, we assessed the role of GPI/AMF as a prognostic factor for clear cell renal cell carcinoma (ccRCC) cancer-specific (CSS) and progression-free survival (PFS). In addition, we evaluated the expression and localization of GPI/AMF and AMFR, using tissue microarray-based immunohistochemistry (TMA-IHC), indirect immunofluorescence (IF), and confocal microscopy analysis.Primary renal tumor and nonneoplastic tissues were collected from 180 patients who underwent nephrectomy for ccRCC. TMA-IHC and IF staining showed an increased signal for both GPI and AMFR in cancer cells, and their colocalization on plasma membrane. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high versus low GPI expression. In particular, patients with high tissue levels of GPI had a 5-year survival rate of 58.8%, as compared to 92.1% for subjects with low levels (P < 0.0001). Similar findings were observed for PFS (56.8% vs 93.3% at 5 years). At multivariate analysis, GPI was an independent adverse prognostic factor for CSS (HR = 1.26; P = 0.001), and PFS (HR = 1.16; P = 0.01).In conclusion, our data suggest that GPI could serve as a marker of ccRCC aggressiveness and a prognostic factor for CSS and PFS.
authors.affiliation: From the Department of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari (GL, MR, VG, AG, SP, CB, PD, MB); Department of Pathology, University of Foggia, Foggia (FS, SC, PB); Department of Pathology, University of Bari (EM); Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari, Bari (DR); Department of Medical and Surgical Sciences, Clinical Pathology Unit, University of Foggia, Foggia (ER); Department of Emergency and Organ Transplantation-Nephrology, Dialysis and Transplantation Unit, University of Bari, Bari (MG, GL); Department of Urology, European Institute of Oncology, Milan (MF, OdC); and Department of Clinical Medicine, Medical Oncology Unit, Federico II University, Naples, Italy (CB, GDL, SDP).
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lucarelli
authors.forename: Monica
authors.initials: M
authors.lastname: Rutigliano
authors.forename: Francesca
authors.initials: F
authors.lastname: Sanguedolce
authors.forename: Vanessa
authors.initials: V
authors.lastname: Galleggiante
authors.forename: Andrea
authors.initials: A
authors.lastname: Giglio
authors.forename: Simona
authors.initials: S
authors.lastname: Cagiano
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Bufo
authors.forename: Eugenio
authors.initials: E
authors.lastname: Maiorano
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.forename: Elena
authors.initials: E
authors.lastname: Ranieri
authors.forename: Margherita
authors.initials: M
authors.lastname: Gigante
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.forename: Matteo
authors.initials: M
authors.lastname: Ferro
authors.forename: Ottavio
authors.initials: O
authors.lastname: de Cobelli
authors.forename: Carlo
authors.initials: C
authors.lastname: Buonerba
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Lorenzo
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
authors.forename: Silvano
authors.initials: S
authors.lastname: Palazzo
authors.forename: Carlo
authors.initials: C
authors.lastname: Bettocchi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Ditonno
authors.forename: Michele
authors.initials: M
authors.lastname: Battaglia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007668:Kidney / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; C554959:GPI protein, human; D005956:Glucose-6-Phosphate Isomerase