Expression and clinical significance of NEDD9 in lung tissues

Neural precursor cell expressed, developmentally downregulated 9 (NEDD9) acts as a scaffold protein and belongs to a family of CAS (Crk-associated substrate) that regulates protein complexes controlling invasion and differentiation. Preclinical research for this gene was predominantly reported in melanomas, glioblastoma, and lymphoma. So we investigated the expression and significance of NEDD9 mRNA and protein in lung tissues. Specifically, we immunohistochemically compared NEDD9 expression and localization in 24 formalin-fixed and paraffin-embedded lung adenocarcinoma tissues with that of surrounding nonneoplastic tissue and five microscopically normal lungs. NEDD9 mRNA levels were quantitatively analyzed by fluorescent quantitative reverse transcription-polymerase chain reaction (FQ-PCR) in frozen tissue specimens of all tumors and 24 matched nonneoplastic lung parenchymas, and protein expression in 16 homogenates of matched neoplastic/nonneoplastic specimens was evaluated by Western blotting. The three techniques showed that NEDD9 is weakly expressed in nonneoplastic lung parenchyma and upregulated in lung adenocarcinoma. Moreover, FQ-PCR indicated a statistically significant correlation between NEDD9 upregulation and higher disease stages (I+II versus III+IV, p=0.001; high and middle versus low differentiation, p<0.001). Our results provide evidence that NEDD9 is upregulated in lung adenocarcinoma, and overexpression of NEDD9 protein has been strongly correlated with staging and differentiation grade and tumor size in lung adenocarcinoma, which demonstrated a poor prognosis.