AIMS: Histone methyltransferase G9a has been primarily understood as a co-repressor of gene expression, but it has been shown that G9a also positively regulates nuclear receptor-mediated transcription. MCM7, a critical component of the DNA replication licensing complex, is amplified and overexpressed in a variety of human malignancies. The objectives of the present study were to study the relationship between the expression of G9a and MCM7 and the pathological grade, clinical stage and prognosis of oesophageal squamous cell carcinoma (OSCC). METHODS AND RESULTS: We collected 139 formalin-fixed and paraffin-embedded tissues from patients with OSCC and surveyed them by tissue microarray-based immunohistochemical staining. Associations between the expression of MCM7 and G9a and clinicopathological parameters and prognosis of OSCC were examined. From tissue microarray immunohistochemistry staining results, we found that nuclear staining intensity for MCM7 and G9a was associated with histological grade (both P < 0.001), tumour depth (P = 0.050, 0.034), lymph node metastasis (P = 0.001, 0.009) and tumour stage (P < 0.001, =0.003). G9a expression was correlated with that of MCM7. G9a overexpression independently predicted poor cancer-specific survival in OSCC (hazard ratio 0.05, 95% confidence interval 0.006-0.417, P = 0.006) and MCM7 (hazard ratio 0.05, 95% confidence interval 0.013-0.441, P = 0.004). OSCC patients whose tumours showed double-positive expression of G9a and MCM7 (G9a(+) MCM7(+) ) had much shorter survival than those from either the G9a or MCM7 low expression groups (G9a(-) MCM7(-) , G9a(+) MCM7(-) , G9a(-) MCM7(+) ). CONCLUSIONS: MCM7 and G9a may serve as effective prognostic factors and could also be used as biomarkers for predicting various clinical outcomes of OSCCs in the Chinese population.
AIMS: Histone methyltransferase G9a has been primarily understood as a co-repressor of gene expression, but it has been shown that G9a also positively regulates nuclear receptor-mediated transcription. MCM7, a critical component of the DNA replication licensing complex, is amplified and overexpressed in a variety of humanmalignancies. The objectives of the present study were to study the relationship between the expression of G9a and MCM7 and the pathological grade, clinical stage and prognosis of oesophageal squamous cell carcinoma (OSCC). METHODS AND RESULTS: We collected 139 formalin-fixed and paraffin-embedded tissues from patients with OSCC and surveyed them by tissue microarray-based immunohistochemical staining. Associations between the expression of MCM7 and G9a and clinicopathological parameters and prognosis of OSCC were examined. From tissue microarray immunohistochemistry staining results, we found that nuclear staining intensity for MCM7 and G9a was associated with histological grade (both P < 0.001), tumour depth (P = 0.050, 0.034), lymph node metastasis (P = 0.001, 0.009) and tumour stage (P < 0.001, =0.003). G9a expression was correlated with that of MCM7. G9a overexpression independently predicted poor cancer-specific survival in OSCC (hazard ratio 0.05, 95% confidence interval 0.006-0.417, P = 0.006) and MCM7 (hazard ratio 0.05, 95% confidence interval 0.013-0.441, P = 0.004). OSCC patients whose tumours showed double-positive expression of G9a and MCM7 (G9a(+) MCM7(+) ) had much shorter survival than those from either the G9a or MCM7 low expression groups (G9a(-) MCM7(-) , G9a(+) MCM7(-) , G9a(-) MCM7(+) ). CONCLUSIONS:MCM7 and G9a may serve as effective prognostic factors and could also be used as biomarkers for predicting various clinical outcomes of OSCCs in the Chinese population.
Authors: Minmin Liu; Stacey L Thomas; Ashley K DeWitt; Wanding Zhou; Zachary B Madaj; Hitoshi Ohtani; Stephen B Baylin; Gangning Liang; Peter A Jones Journal: Cancer Res Date: 2018-09-05 Impact factor: 12.701