Identification of biomarkers for lymph node metastasis in early-stage cervical cancer by tissue-based proteomics

Background: Pelvic lymph node metastasis (PLNM) is the key to determining the treatment and prognosis of early-stage cervical cancer (CC, I-IIst). The aim of this study was to identify biomarkers for PLNM of CC, I-IIst. Methods: Two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption/ionisation-time-of-flight mass spectrometry (MALDI-TOF/TOF MS) were used to identify differentially expressed proteins in primary CC, I-IIst tissue with (n=8) and without (n=10) PLNM. The expression levels of three differential proteins (FABP5, HspB1, and MnSOD) were validated using western blotting and immunohistochemistry. An independent cohort of 105 CC, I-IIst patients was analysed to assess the correlation of FABP5, HspB1, and MnSOD with clinicopathologic factors and clinical outcomes. Results: Forty-one differential proteins were identified. Upregulation of FABP5, HspB1, and MnSOD in CC, I-IIst with PLNM was confirmed and was significantly correlated with PLNM. FABP5, HspB1, and MnSOD were significant predictors of PLNM in univariate analysis. FABP5, HspB1, and lymphovascular space invasion (LVSI) were independent predictors of PLNM in multivariate analysis. Survival curves indicated that CC, I-IIst patients with FABP5, HspB1, and MnSOD upregulation had poor prognosis. Conclusions: FABP5, HspB1, and MnSOD may be potential biomarkers for PLNM of CC, I-IIst and may have important roles in the pathogenesis of PLNM.