title: Overexpression of G9a and MCM7 in oesophageal squamous cell carcinoma is associated with poor prognosis.
abstract: OBJECTIVE
  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).
  
  
  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.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Zhong
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Chen
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Guan
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.forename: Yinan
authors.initials: Y
authors.lastname: Ma
authors.forename: Shuguang
authors.initials: S
authors.lastname: Zhang
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006649:Histocompatibility Antigens / Q000096:biosynthesis*; D011495:Histone-Lysine N-Methyltransferase / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D064168:Minichromosome Maintenance Complex Component 7 / Q000096:biosynthesis*; D011379:Prognosis; D034741:RNA, Small Interfering; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D006649:Histocompatibility Antigens; D034741:RNA, Small Interfering; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7
keywords: G9a; MCM7; oesophageal squamous cell carcinoma; prognosis