Suppression of Zinc Finger Homeobox 3 expression in tumor cells decreases the survival rate among non-small cell lung cancer patients.

Zinc Finger Homeobox 3 (ZFHX3) was first identified as a suppressor of alpha-fetoprotein gene and is a good candidate for the 16q22 tumor suppressor. In this study we investigated the relationship between tumoral ZFHX3 mRNA expression and the clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). We used semi-quantitative real time reverse transcription polymerase chain reaction to assess expression of ZFHX3 mRNA in tumor samples from 140 patients with NSCLC. We found that the 5-year overall survival rate among patients weakly expressing ZFHX3 was significantly poorer than among those expressing higher levels of ZFHX3 (P< 0.0001 by log-rank test). Multivariate logistic regression analysis revealed being lower ZFHX3 expression are independent predictors of lymph node metastasis. With low-ZFHX3 tumors, there was a significantly (P=0.009) greater (7.39-fold higher) risk of lymph node metastasis. Multivariate Cox proportional hazard analyses revealed that being lower ZFHX3 expression (Hazard ratio, 4.42; 95% CI, 2.09-8.92; p=0.0002) were independent factors affecting 5-year overall survival. Ratio of ZFHX3 mRNA in tumor against normal lung in low-ZFHX3 tumor was lower than in high-ZFHX3 tumor. In conclusion, suppression of ZFHX3 expression in tumor cells decreases the survival rate among patients with NSCLC.