Am J Cancer Res 2013;3(5): 509-517
Original Article
Histone demethylase GASC1, a potential prognostic and predictive marker in
esophageal squamous cell carcinoma
Ling-Ling Sun, Andreana Holowatyj, Xiu-E Xu, Jian-Yi Wu, Zhi-Yong Wu, Jin-Hui Shen, Shao-Hong Wang, En-Min Li, Zeng-Quan
Yang, Li-Yan Xu
Institute of Oncologic Pathology, Department of Biochemistry and Molecular Biology, The Key Laboratory of Molecular Biology for
High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China; Department of Oncology,
Karmanos Cancer Institute, Wayne State University, Detroit, USA; Departments of Oncology Surgery, Pathology, Shantou Central
Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, China
Received September 7, 2013; Accepted October 5, 2013; Epub November 1, 2013; Published November 15, 2013
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. (ajcr0000226).
Keywords: Histone demethylase, GASC1, lymph node metastasis, immunohistochemistry, esophageal squamous cell
carcinoma
Address correspondence to: Li-Yan Xu, Institute of Oncologic Pathology, Medical College of Shantou University, No. 22, Xinling
Road, Shantou, Guangdong 515041, China. Tel: +86-754-88900460; Fax: +86-754-88900847; E-mail: lyxu@stu.edu.cn;
Zeng-Quan Yang, Department of Oncology, Karmanos Cancer Institute, Wayne State University, USA. E-mail:
yangz@karmanos.org; En-Min Li, Department of Biochemistry and Molecular Biology, The Key Laboratory of Molecular Biology for
High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, China. E-mail: nmli@stu.edu.cn
Original Article
Histone demethylase GASC1, a potential prognostic and predictive marker in
esophageal squamous cell carcinoma
Ling-Ling Sun, Andreana Holowatyj, Xiu-E Xu, Jian-Yi Wu, Zhi-Yong Wu, Jin-Hui Shen, Shao-Hong Wang, En-Min Li, Zeng-Quan
Yang, Li-Yan Xu
Institute of Oncologic Pathology, Department of Biochemistry and Molecular Biology, The Key Laboratory of Molecular Biology for
High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China; Department of Oncology,
Karmanos Cancer Institute, Wayne State University, Detroit, USA; Departments of Oncology Surgery, Pathology, Shantou Central
Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, China
Received September 7, 2013; Accepted October 5, 2013; Epub November 1, 2013; Published November 15, 2013
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. (ajcr0000226).
Keywords: Histone demethylase, GASC1, lymph node metastasis, immunohistochemistry, esophageal squamous cell
carcinoma
Address correspondence to: Li-Yan Xu, Institute of Oncologic Pathology, Medical College of Shantou University, No. 22, Xinling
Road, Shantou, Guangdong 515041, China. Tel: +86-754-88900460; Fax: +86-754-88900847; E-mail: lyxu@stu.edu.cn;
Zeng-Quan Yang, Department of Oncology, Karmanos Cancer Institute, Wayne State University, USA. E-mail:
yangz@karmanos.org; En-Min Li, Department of Biochemistry and Molecular Biology, The Key Laboratory of Molecular Biology for
High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, China. E-mail: nmli@stu.edu.cn
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American Journal of Cancer Research
| ISSN: 2156-6976 |