Objectives: Proteomic profiling of serum is an emerging technique to identify new biomarkers indicative of disease severity and progression. Our study was to assess the use of surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify multiple serum protein biomarkers for early detection of laryngeal squamous cell carcinoma (LSCC), establish predictive model, and accurately distinguish LSCC patients with or without lymph node metastasis.
Methods: A cohort of 252 serum samples with LSCC (n = 142) and normal control (n = 110) were consented into this study. These serum samples were randomly divided into training set (including 89 LSCC patients at stages I-II and 65 normal controls, 30 LSCC patients with lymph node metastasis) and blind testing set (including 53 LSCC patients at stages III-IV and 45 normal controls). Serum protein profiles on weak cationic exchange (WCX2) were performed by SELDI-TOF MS and then analyzed by Biomarker Wizard software. The Decision Tree classification algorithm and blind validation were determined by Biomarker Pattern Software (BPS).
Results: A panel of 18 biomarkers ranging 2-30 kDa was selected based on their collective contribution to the optimal separation between stages I-II LSCC patients and healthy controls. Among them, one candidate protein peak with an m/z value of 4,176 Da was selected to establish predictive model by BPS with sensitivity of 86.52% and specificity of 84.62%. The ability to detect LSCC patients was evaluated using blinding test data in stages III and IV cancer patients. A sensitivity of 84.91% and specificity of 82.22% were validated in blind testing set. Meanwhile 14 potential biomarkers could differentiate LSCC patients with or without lymph node metastasis (P < 0.05).
Conclusions: The high sensitivity and specificity achieved by the serum protein biomarkers show great potential for the early detection of LSCC. SELDI-TOF MS serum profiling also is able to distinguish LSCC patients with or without lymph node metastasis.