title: Circulating Levels of PAI-1 and SERPINE1 4G/4G Polymorphism Are Predictive of Poor Prognosis in HCC Patients Undergoing TACE.
abstract: Although several molecular markers have been proposed as prognostic of disease progression in Hepatocellular carcinoma (HCC), predictive markers of response to treatment are still unsatisfactory. Here, we propose a genetic polymorphism as a potential predictive factor of poor prognosis in HCC patients treated with transcatheter arterial chemoembolization (TACE). In particular, we show that the guanosine insertion/deletion polymorphism in the promoter region of SERPINE1 gene at the -675 bp position, named 4G/4G, predicts poor prognosis in a cohort of 75 patients with HCC undergoing TACE. By a combination of ELISA and SERPINE1 promoter study, we found that the presence of elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) in patients with 4G/4G genotype is significantly associated with reduced overall survival compared to patients with 5G/5G or 4G/5G genotype in HCC patients after TACE. Our analysis provided evidence that variation in SERPINE1 gene plays a role in defining the outcome in patients treated with TACE. In addition to a poor disease outcome, the 4G/4G variant represents an unfavorable predictive factor for response to chemotherapy as well.
authors: Clinical Pathology Laboratory, Department of Experimental Oncology, Giovanni Paolo II National Cancer Institute, Bari, Italy. Electronic address: rosadive@inwind.it.
authors: Rosa
authors: R
authors: Divella
authors: Clinical Pathology Laboratory, Department of Experimental Oncology, Giovanni Paolo II National Cancer Institute, Bari, Italy.
authors: Antonella
authors: A
authors: Daniele
authors: Clinical Pathology Laboratory, Department of Experimental Oncology, Giovanni Paolo II National Cancer Institute, Bari, Italy.
authors: Ines
authors: I
authors: Abbate
authors: Clinical Pathology Laboratory, Department of Experimental Oncology, Giovanni Paolo II National Cancer Institute, Bari, Italy.
authors: Eufemia
authors: E
authors: Savino
authors: Clinical Pathology Laboratory, Department of Experimental Oncology, Giovanni Paolo II National Cancer Institute, Bari, Italy.
authors: Porzia
authors: P
authors: Casamassima
authors: Clinical Pathology Laboratory, Department of Experimental Oncology, Giovanni Paolo II National Cancer Institute, Bari, Italy.
authors: Giancarlo
authors: G
authors: Sciortino
authors: Department of Pathology, Giovanni Paolo II National Cancer Institute, Bari, Italy.
authors: Giovanni
authors: G
authors: Simone
authors: Hospital "Monsignor Raffaele Dimiccoli", Barletta, Italy.
authors: Gennaro
authors: G
authors: Gadaleta-Caldarola
authors: Unit of Interventional Radiology, Department of Critical Area and Surgery, Giovanni Paolo II National Cancer Institute, Bari, Italy.
authors: Vito
authors: V
authors: Fazio
authors: Unit of Interventional Radiology, Department of Critical Area and Surgery, Giovanni Paolo II National Cancer Institute, Bari, Italy.
authors: Cosimo Damiano
authors: CD
authors: Gadaleta
authors: Interdisciplinary Department of Medicine, University of Bari School of Medicine, Bari, Italy.
authors: Carlo
authors: C
authors: Sabbà
authors: Interdisciplinary Department of Medicine, University of Bari School of Medicine, Bari, Italy; IRCCS "S. de Bellis", National Institute for Digestive Diseases, Bari, Italy. Electronic address: a.mazzocca@intmed.uniba.it.
authors: Antonio
authors: A
authors: Mazzocca