Diversity of Clinical Implication of B-Cell Translocation Gene 1 Expression by Histopathologic and Anatomic Subtypes of Gastric Cancer

作者：Kanda Mitsuro^*; Oya Hisaharu; Nomoto Shuji; Takami Hideki; Shimizu Dai; Hashimoto Ryoji; Sueoka Satoshi; Kobayashi Daisuke; Tanaka Chie; Yamada Suguru; Fujii Tsutomu; Nakayama Goro; Sugimoto Hiroyuki; Koike Masahiko; Fujiwara Michitaka; Kodera Yasuhiro

来源：Digestive Diseases and Sciences, 2015, 60(5): 1256-1264.

DOI：10.1007/s10620-014-3477-8

• B-cell translocation gene 1
• Gastric cancer
• Expression
• Subtype

Background Genetic signatures may differ by histopathologic and anatomic subtypes of gastric cancer (GC). B-cell translocation gene 1 (BTG1) was identified as one of genes downregulated in GC tissues from our microarray data.
Aims To evaluate the clinical implications of BTG1 expression in GC and the genetic diversity among GC subtypes.
Methods BTG1 mRNA expression was analyzed in GC cell lines and 233 pairs of surgical specimens. The mutational and methylation status of BTG1 in GC cell lines was analyzed, and immunohistochemistry was conducted to determine the distribution of BTG1. The pattern and prognostic significance of BTG1 expression were correlated with the three proposed GC subtypes.
Results BTG1 mRNA was downregulated in 82 % of GC cell lines and in 88 % of clinical GC tissues. Promoter hypermethylation events or sequence mutations were not detected in GC cell lines. The pattern of BTG1 expression as observed by immunohistochemistry was consistent with that of its mRNA. Downregulation of BTG1 mRNA in GCs was significantly associated with shorter disease-specific and recurrence-free survival. Multivariate analysis of disease-specific survival identified downregulation of BTG1 transcription as an independent prognostic factor. BTG1 mRNA expression was more strongly suppressed in proximal nondiffuse and diffuse GC compared with distal nondiffuse GC, and subgroup analysis revealed that BTG1 downregulation led to adverse prognosis, specifically in patients with proximal nondiffuse and diffuse GC.
Conclusions Altered expression of BTG1 is a potential biomarker for carcinogenesis and progression of GC, particularly for proximal nondiffuse and diffuse GC.

• 出版日期2015-5