Suppressor gene GRHL1 is associated with prognosis in patients with oesophageal squamous cell carcinoma

Grainyhead like transcription factor 1 (GRHL1) is among the key family genes encoding transcription factors that serve important roles in inhibiting tumor cell clone growth, proliferation and the progression of embedded tumor cells. The present study aimed to investigate the expression and prognostic value of GRHL1 in oesophageal squamous cell carcinoma (ESCC). GRHL1 mRNA and protein levels were detected in ESCC cell lines and clinical ESCC tissues. The expression of GRHL1 was detected by immunohistochemistry in 266 formalin-fixed paraffin-embedded ESCC samples with the help of Pearson's χ2 test, and Cox regression analysis was employed in order to distinguish independent prognostic factors. The functional role of GRHL1 in ESCC cell lines was assessed by a lentiviral construct containing overexpressed GRHL1, which was then examined by cell growth and foci formation assays. The expression of GRHL1 was downregulated in the majority of examined ESCC cell lines and clinical tissues at the mRNA and protein levels. In addition, Kaplan-Meier analysis demonstrated that the low expression of GRHL1 was fundamentally associated with a reduced overall survival rate (log-rank test, P<0.001, hazard ratio, 2.073; 95% confidence interval, 1.491–2.881). Additionally, Cox regression analysis revealed that the low expression of GRHL1, together with poor differentiation, constituted independent prognostic factors for the poor survival of patients with ESCC (P<0.05). The results indicated that the GRHL1-overexpressing cells attenuated the invasive capacity of the ESCC cells in vitro. Accordingly, the low expression of GRHL1 is associated with a reduced OS in ESCC, and the overexpression of GRHL1 inhibited cell invasion in ESCC cells. The results of the present study indicated that GRHL1 may serve as a prognostic marker, in addition to being a novel potential target gene for ESCC.