Clinical significance of GADD153 expression in stage I non-small cell lung cancer

Abstract

The transcription factor growth arrest and DNA damage-inducible gene 153 (GADD153), also known as CHOP, is considered to function as a proapoptotic molecule. Overexpression of GADD153 leads to cell cycle arrest and/or apoptosis. However, its clinical implications in non-small cell lung cancer (NSCLC) remain controversial. Therefore, we investigated the expression of GADD153 in stage I NSCLC using immunohistochemistry. Paraffin-embedded tissue sections from 76 patients, who were diagnosed with primary stage I NSCLC and had undergone a curative lung resection, were stained using an anti-GADD153 antibody. The intensity of GADD153 immunostaining was evaluated within the cell membrane and cytoplasm of invasive cancer components. The correlation between the intratumoral expression of GADD153 and various clinical parameters were explored. GADD153 was detected in 29 (38.2%) cases. No statistically significant difference in expression was demonstrated between stage IA and stage IB tumors (35.0 vs. 39.3%; P=0.735). The expression of GADD153 was not affected by histological subtypes or histological grades of differentiation. The intratumoral expression of GADD153 did not influence the overall survival rate (53.29 vs. 52.18 months; P=0.743) or disease-free survival rate (46.97 vs. 54.19 months; P=0.084) of stage I NSCLC patients. However, patients with GADD153 expression demonstrated an improved disease-specific survival rate (28.80 vs. 53.85 months; P=0.020). No patients with GADD153 expression demonstrated distant metastasis (P=0.029). These data suggest that GADD153 expression may be a valuable prognostic factor of early-stage NSCLC in patients who have undergone curative lung resection.

Figure 1

GADD153 expression in NSCLC tissue. (A) Adenocarcinoma and (B) squamous cell carcinoma of the lung demonstrate strong immunoreactivity with GADD153. (C) Bronchioloalveolar carcinoma demonstrates positive GADD153 expression (magnification, ×200). GADD153, growth arrest and DNA damage-inducible gene 153; NSCLC, non-small cell lung cancer.

Figure 2

Survival analysis of stage I NSCLC patients according to GADD153 expression. Patients whose tumors expressed GADD153 had a significantly improved disease-specific survival compared to those without GADD153 expression (P=0.02). GADD153, growth arrest and DNA damage-inducible gene 153; NSCLC, non-small cell lung cancer.