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.
Medicine. 2015 Nov [Epub]
Giuseppe Lucarelli, Monica Rutigliano, Francesca Sanguedolce, Vanessa Galleggiante, Andrea Giglio, Simona Cagiano, Pantaleo Bufo, Eugenio Maiorano, Domenico Ribatti, Elena Ranieri, Margherita Gigante, Loreto Gesualdo, Matteo Ferro, Ottavio de Cobelli, Carlo Buonerba, Giuseppe Di Lorenzo, Sabino De Placido, Silvano Palazzo, Carlo Bettocchi, Pasquale Ditonno, Michele Battaglia
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).