title: Novel predictive biomarkers for cervical cancer prognosis.
abstract: High hypoxic, glycolytic and acidosis metabolisms characterize cervical cancer tumors and have been described to be involved in chemoradioresistance mechanisms. Based on these observations, the present study assessed four selected novel biomarkers on the prognosis of locally advanced cervical carcinoma. A total of 66 patients with stage IIB/IIIB cervical cancer were retrospectively included. The protein expression levels of glucose transporter 1 (GLUT1), carbonic anhydrase 9 (CAIX) and hexokinase 1 (HKII) were investigated by immunohistochemistry on tumor biopsies, hemoglobin was measured and the disease outcome was monitored. A total of 53 patients (80.3%) presented a complete response. For these patients, the protein expression levels of GLUT1, CAIX and HKII were overexpressed. A significant difference was observed (P=0.0127) for hemoglobin levels (≤11 g/dl) in responsive compared with non-responsive patients. The expression of GLUT1 is associated with a lower rate of both overall and disease-free survival, with a trend of decreased risk of 1.1x and 1.5x, respectively. Co-expression of GLUT1 and HKII is associated with a decreased trend risk of 1.6x for overall survival. Patients with hemoglobin levels ≤11 g/dl had a 4.3-fold risk (P=0.02) in decreasing both to the rate of overall and disease-free survival. The presence of anemic hypoxia (hemoglobin ≤11 g/dl) and the expression of GLUT1 and/or HKII influence treatment response and are associated with a lower overall and disease-free survival. The present results demonstrated that these biomarkers may be used as predictive markers and suggested that these metabolic pathways can be used as potential novel therapeutic targets.
authors.affiliation: Research Group in Cancer Biology, Research Group in Radiobiology Clinical, Molecular and Celular, National Cancer Institute, Bogotá, Colombia.
authors.forename: Pablo
authors.initials: P
authors.lastname: Moreno-Acosta
authors.affiliation: Research Group in Cancer Biology, Research Group in Radiobiology Clinical, Molecular and Celular, National Cancer Institute, Bogotá, Colombia.
authors.forename: Schyrly
authors.initials: S
authors.lastname: Carrillo
authors.affiliation: Analysis Unit, National Cancer Institute, Bogotá, Colombia.
authors.forename: Oscar
authors.initials: O
authors.lastname: Gamboa
authors.affiliation: Pathological Oncology Group, National Cancer Institute, Bogotá, Colombia.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Romero-Rojas
authors.affiliation: Pathology Group, National University of Colombia, Bogotá, Colombia.
authors.forename: Jinneth
authors.initials: J
authors.lastname: Acosta
authors.affiliation: Microbiology and Infection Diseases, The Royal Women's Hospital, Melbourne, Victoria, Australia.
authors.forename: Monica
authors.initials: M
authors.lastname: Molano
authors.affiliation: Radiation Oncology Department, SanPau Hospital, Barcelona, Spain.
authors.forename: Joseph
authors.initials: J
authors.lastname: Balart-Serra
authors.affiliation: Department of Radiotherapy, National Cancer Institute, Bogotá, Colombia.
authors.forename: Martha
authors.initials: M
authors.lastname: Cotes
authors.affiliation: Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest En Jarez, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Rancoule
authors.affiliation: Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest En Jarez, France; Laboratory of Radiobiology, EMR3738, Faculty of Medicine Lyon Sud, Pierre Bénite, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Magné
keywords: anemic hypoxia; biomarkers; carbonic anhydrase IX; cervical cancer; glucose transporter type 1; hexokinase