Histone demethylase GASC1, a potential prognostic and predictive marker in esophageal squamous cell carcinoma

Abstract

Gene amplified in squamous cell carcinoma 1 (GASC1) is a member of Jumonji C-domain containing histone demethylases that play an essential role in affecting chromatin architecture and gene expression. The purpose of this study was to determine the expression features and the clinical significance of GASC1 in esophageal squamous cell carcinoma (ESCC). GASC1 expression was detected on tissue microarrays of ESCC samples in 185 cases using immunohistochemical staining. Strong nuclear staining for GASC1 was observed in a subset of ESCC samples. The nuclear expression of GASC1 was significantly associated with lymph node metastasis (P=0.030) and tumor-node metastasis stages (P=0.013). Kaplan-Meier survival analysis showed a tendency that high expression of GASC1 in the nucleus was associated with poor survival of ESCC patients, with a 5-year survival rate of 26.5%, as compared to 43.7% for patients with GASC1-negative/low expression. Furthermore, multivariate analysis revealed that high expression of GASC1 likely acts as a predictive factor for overall survival of ESCC patients, despite the P-value failing to reach significance (P=0.059). The findings indicate that histone demethylase GASC1 may play an important role in promoting cancer metastasis, and shed new light on the importance of targeting GASC1 to suppress metastatic disease in various tumor types, including ESCC.

Keywords: GASC1; Histone demethylase; esophageal squamous cell carcinoma; immunohistochemistry; lymph node metastasis.

Figures

Figure 1

Results of immunohistochemical staining for GASC1. A: Strong immunoreactivity for GASC1 was observed in the nucleus of one repressive ESCC sample. B: Strong nuclear staining was also found in the cases of carcinoma in situ, while, C: weak or moderate GASC1 nuclear staining was observed in adjacent non-tumorigenic esophageal epithelium. A-C are all magnified versions (×400) of the corresponding embedded micrographs on the left (×200). The bar: 50 μm.

Figure 2

Overall survival of the patients with ESCC in relation to the expression level of GASC1 in the nucleus. Kaplan-Meier survival curve showing that patients with ESCC expressing high nuclear GASC1 have worse survival compared with patients with negative or low GASC1 expressing tumors.