High CD133 expression in the nucleus and cytoplasm predicts poor prognosis in non-small cell lung cancer

Abstract

Objective: The aim of this study was to investigate the expression of Prominin-1 (CD133) in cancer cells and its potential value as a prognostic indicator of survival in patients with non-small cell lung cancer (NSCLC).

Methods: Cancerous tissues and matched normal tissues adjacent to the carcinoma from 239 NSCLC patients were obtained immediately after surgery. Immunohistochemistry of tissue microarrays was used to characterize the expression of CD133 in NSCLC and adjacent tissues. The correlation of CD133 expression with clinical characteristics and prognosis was determined by statistical analysis.

Results: CD133 protein expression levels in both the cytoplasm and nucleus were significantly higher in NSCLC tissues compared with corresponding peritumoral tissue (P < 0.05). CD133 expression in the nucleus of NSCLC cells was related to tumor diameter (P = 0.027), tumor differentiation (P < 0.001), and TNM stage (P = 0.007). Kaplan-Meier survival and Cox regression analyses revealed that high CD133 expression in the nucleus was an independent predictor of poor prognosis of NSCLC, as was high cytoplasmic CD133 expression (P < 0.001).

Conclusion: Our findings provide the first evidence that high expression of CD133 in both the nucleus and cytoplasm is associated with poor prognosis in NSCLC.

Figure 1

Representative patterns of CD133 protein expression in NSCLC and normal lung tissue. (a1) and (a2) Adenocarcinoma tissue and adjacent normal lung tissue. The expression of CD133 in tumor tissue was higher than that in adjacent normal lung tissue by IHC staining. The red arrow indicates positive CD133 protein expression in the nucleus of adenocarcinoma cells. The green arrow indicates strong CD133 staining in the cytoplasm of tumor cells. (b1) and (b2) Squamous cell carcinoma of the lung. The expression of CD133 protein was positive in lung carcinoma tissues. The red arrow indicates positive CD133 protein expression in the nucleus of tumor cells. (c1) and (c2) Squamous cell carcinoma of the lung. The green arrow indicates CD133 staining in the cytoplasm of tumor cells. (d1) and (d2) Normal lung tissue. The expression of CD133 protein was negative in both the cytoplasm and nucleus. The yellow arrow indicates that expression of CD133 in alveolar epithelial cells is negative.

Figure 2

Kaplan-Meier survival curves following surgical therapy in NSCLC. (a) Patients with high CD133 expression in the nucleus of tumor cells (green line) exhibited significantly poorer survival compared with the low or no expression group (blue line). (b) Patients with high CD133 expression in the cytoplasm of tumor cells (green line) exhibited significantly poorer survival compared with the low or no expression group (blue line).