title: High BAX/BCL2 mRNA ratio predicts favorable prognosis in laryngeal squamous cell carcinoma, particularly in patients with negative lymph nodes at the time of diagnosis.
abstract: OBJECTIVE
  Laryngeal squamous cell carcinoma (LSCC), a common type of head and neck cancer, is associated with high rates of metastasis and recurrence. Therefore, accurate prognostic stratification of LSCC patients based on molecular prognostic tumor biomarkers would definitely lead to a better clinical management of this malignancy. The aim of this study was the investigation of the potential combinatorial prognostic value of BCL2 and BAX mRNA expression in LSCC.
  
  
  METHODS
  Total RNA was isolated from 105 cancerous laryngeal tissue specimens obtained from patients having undergone surgical treatment for primary LSCC. After cDNA preparation, a low-cost, in-house developed, sensitive and accurate real-time quantitative PCR (qPCR) methodology was applied for the quantification of BCL2 and BAX mRNA levels. Then, we carried out a biostatistical analysis to assess the prognostic value of the BAX/BCL2 mRNA expression ratio.
  
  
  RESULTS
  High BAX/BCL2 mRNA expression constitutes a favorable prognosticator in LSCC, predicting significantly longer disease-free survival (P=0.011) and overall survival (P=0.014) of patients. More importantly, the significant prognostic value of the BAX/BCL2 mRNA expression appeared to be independent of the histological grade and size of the malignant laryngeal tumor as well as TNM stage, as revealed by the multivariate bootstrap Cox regression analysis. Kaplan-Meier survival analysis demonstrated also that the BAX/BCL2 ratio can stratify node-negative (N0) LSCC patients into two subgroups with significantly different DFS and OS (P=0.021 and P=0.009, respectively).
  
  
  CONCLUSIONS
  The BAX/BCL2 mRNA ratio is a putative molecular tissue biomarker in CLL and hence deserves further validation in larger cohorts of LSCC patients.
authors.affiliation: First Department of Otorhinolaryngology, Athens General Hospital "Hippokration", National and Kapodistrian University of Athens, Athens GR-11527, Greece.
authors.forename: Aris I
authors.initials: AI
authors.lastname: Giotakis
authors.affiliation: Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Athens GR-15701, Greece.
authors.forename: Christos K
authors.initials: CK
authors.lastname: Kontos
authors.affiliation: First Department of Otorhinolaryngology, Athens General Hospital "Hippokration", National and Kapodistrian University of Athens, Athens GR-11527, Greece.
authors.forename: Leonidas D
authors.initials: LD
authors.lastname: Manolopoulos
authors.affiliation: First Department of Otorhinolaryngology, Athens General Hospital "Hippokration", National and Kapodistrian University of Athens, Athens GR-11527, Greece.
authors.forename: Aristides
authors.initials: A
authors.lastname: Sismanis
authors.affiliation: First Department of Propaedeutic Surgery, Athens General Hospital "Hippokration", National and Kapodistrian University of Athens, Athens GR-11527, Greece.
authors.forename: Manousos M
authors.initials: MM
authors.lastname: Konstadoulakis
authors.affiliation: Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Athens GR-15701, Greece. Electronic address: ascorilas@biol.uoa.gr.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein
keywords: BCL2 family; Head and neck cancer; Molecular tumor biomarker; Oral cancer; Prognostic biomarker; Real-time quantitative PCR