Diversity of clinical implication of B-cell translocation gene 1 expression by histopathologic and anatomic subtypes of gastric cancer.

Abstract

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.

• Authors: Mitsuro Kanda, Hisaharu Oya, Shuji Nomoto, Hideki Takami, Dai Shimizu, Ryoji Hashimoto, Satoshi Sueoka, Daisuke Kobayashi, Chie Tanaka, Suguru Yamada, Tsutomu Fujii, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 60 Issue 5 Pg. 1256-64 (May 2015) ISSN: 1573-2568 [Electronic] United States
• PMID: 25487193 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Neoplasm Proteins
• RNA, Messenger
• BTG1 protein, human

Topics

• Adenocarcinoma (genetics, metabolism, mortality, pathology, surgery)
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics, metabolism)
• Cell Line, Tumor
• DNA Methylation
• DNA Mutational Analysis
• Disease-Free Survival
• Down-Regulation
• Female
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multivariate Analysis
• Mutation
• Neoplasm Proteins (genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• Promoter Regions, Genetic
• Proportional Hazards Models
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Factors
• Stomach Neoplasms (genetics, metabolism, mortality, pathology, surgery)
• Time Factors
• Transcription, Genetic
• Treatment Outcome
• Young Adult