title: Prognostic cell biological markers in cervical cancer patients primarily treated with (chemo)radiation: a systematic review.
abstract: The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in ≥50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biological markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1α). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.
authors.affiliation: Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Maartje G
authors.initials: MG
authors.lastname: Noordhuis
authors.forename: Jasper J H
authors.initials: JJ
authors.lastname: Eijsink
authors.forename: Frank
authors.initials: F
authors.lastname: Roossink
authors.forename: Pauline
authors.initials: P
authors.lastname: de Graeff
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pras
authors.forename: Ed
authors.initials: E
authors.lastname: Schuuring
authors.forename: G Bea A
authors.initials: GB
authors.lastname: Wisman
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: de Bock
authors.forename: Ate G J
authors.initials: AG
authors.lastname: van der Zee
mesh_terms: D000704:Analysis of Variance; D000951:Antigens, Neoplasm / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D014408:Biomarkers, Tumor / Q000502:physiology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000502:physiology; D049109:Cell Proliferation; D003131:Combined Modality Therapy / Q000379:methods / Q000401:mortality; D051546:Cyclooxygenase 2 / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology; D015843:Serpins / Q000502:physiology; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy
chemical_list: D000951:Antigens, Neoplasm; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018719:Erb-b2 Receptor Tyrosine Kinases; D015843:Serpins; C051072:squamous cell carcinoma-related antigen; C089226:CA9 protein, human