Metastasis is a major cause of cancer recurrence or death. This study attempted to quantitatively identify different proteins in metastatic lung adenocarcinoma. The N/T quotient [number of metastatic lymph nodes (n)/tumor diameter (cm)] was used to select samples with an extreme metastatic phenotype. Among the six fresh frozen lung adenocarcinoma specimens, the three showing the highest N/T quotient represented the metastatic group, and others with the greatest tumor diameters without metastasis represented the non-metastatic group. After 2-dimensional electrophoresis, the significantly different protein spots were selected by image analysis and analyzed with MALDI-TOF mass spectrometry. Acyl-CoA thioesterase 8 isoform c (ACOT8) was one of most overexpressed proteins in the metastatic group, and it was validated by Western blot and immunohistochemical staining on 108 paraffin-embedded tumor samples. High ACOT8 expression was correlated with lymph node metastasis (p=0.002), recurrence (p=0.034), predominant histologic subtypes (p=0.007), and higher stage (p=0.005). In multivariate analysis, high ACOT8 expression was significantly associated with increased risks of lymph node metastasis (p=0.009) and cancer-related death (p=0.030), independent of clinical factors. ACOT8 may be a candidate prognostic biomarker and therapeutic target of lung adenocarcinoma.
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