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

• Published in: Clinical biochemistry 2016-08, Vol.49 (12), p.890-896
• Main Authors: Giotakis, Aris I., Kontos, Christos K., Manolopoulos, Leonidas D., Sismanis, Aristides, Konstadoulakis, Manousos M., Scorilas, Andreas
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; bcl-2-Associated X Protein - genetics; BCL2 family; Biomarkers, Tumor - genetics; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - surgery; Female; Follow-Up Studies; Head and neck cancer; Humans; Laryngeal Neoplasms - genetics; Laryngeal Neoplasms - pathology; Laryngeal Neoplasms - surgery; Lymph Nodes - metabolism; Lymph Nodes - pathology; Male; Middle Aged; Molecular tumor biomarker; Neoplasm Grading; Neoplasm Staging; Oral cancer; Prognosis; Prognostic biomarker; Proto-Oncogene Proteins c-bcl-2 - genetics; Real-Time Polymerase Chain Reaction; Real-time quantitative PCR; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Survival Rate
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/j.clinbiochem.2016.04.010

Objectives: 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. Design and 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. •A low-cost, in-house developed qPCR method was used to quantify BCL2 and BAX mRNA.•High BAX/BCL2 mRNA expression ratio constitutes a favorable prognosticator in LSCC.•High BAX/BCL2 mRNA ratio predicts longer DFS independently of TNM stage and grade.•High BAX/BCL2 mRNA ratio predicts longer OS independently of TNM stage and grade.•The BAX/BCL2 ratio stratifies N0 patients into two distinct prognostic subgroups.