Promoter hypermethylation inactivate tumour suppressor FAM134B and is associated with poor prognosis in colorectal cancer

Islam, Farhadul, Gopalan, Vinod, Pillai, Suja, Lu, Cu-Tai, Kasem, Kais and King-Yin Lam, Alfred (2018) Promoter hypermethylation inactivate tumour suppressor FAM134B and is associated with poor prognosis in colorectal cancer. Genes, Chromosomes and Cancer, 57 5: 240-251. doi:10.1002/gcc.22525


Author Islam, Farhadul
Gopalan, Vinod
Pillai, Suja
Lu, Cu-Tai
Kasem, Kais
King-Yin Lam, Alfred
Title Promoter hypermethylation inactivate tumour suppressor FAM134B and is associated with poor prognosis in colorectal cancer
Formatted title
Promoter hypermethylation inactivate tumour suppressor FAM134B and is associated with poor prognosis in colorectal cancer
Journal name Genes, Chromosomes and Cancer   Check publisher's open access policy
ISSN 1098-2264
1045-2257
Publication date 2018-01-30
Year available 2018
Sub-type Article (original research)
DOI 10.1002/gcc.22525
Open Access Status Not yet assessed
Volume 57
Issue 5
Start page 240
End page 251
Total pages 12
Place of publication Hoboken, NJ United States
Publisher John Wiley & Sons
Language eng
Subject 1311 Genetics
1306 Cancer Research
Abstract The present study aims to examine promoter methylation status of FAM134B in a large cohort of patients with colorectal adenocarcinomas. The clinical significances and correlations of FAM134B promoter methylation with its expression are also analysed. Methylation-specific high-resolution melt-curve analysis followed by sequencing was used to identify FAM134B promoter methylation in colorectal adenomas (n=32), colorectal adenocarcinomas (n=164), matched adjacent non-neoplastic colorectal mucosae (n=83) and colon cancer cell lines (n=4). FAM134B expression was studied by real-time quantitative polymerase chain reaction, immunohistochemistry, and Western blots. FAM134B promoter methylation was more frequent in adenocarcinomas (52%; 85/164) when compared to that of adenomas (28%; 9/32) and non-neoplastic mucosae (35%; 29/83). Cancer cells exhibited higher methylation when compared to non-neoplastic cells. FAM134B promoter methylation was inversely correlated with low FAM134B copy number and mRNA/protein expressions, whereas in-vitro demethylation has restored FAM134B expression in colon cancer cells. FAM134B promoter methylation was associated with high histological grade (p = 0.025), presence of peri-neural infiltration (p = 0.012), lymphovascular invasion (p = 0.021), lymph node metastasis (p = 0.0001), distant metastasis (p = 0.0001) and advanced pathological stages (p = 0.0001). In addition, FAM134B promoter methylation correlated with cancer recurrence and poor survival rates of patients with colorectal adenocarcinomas. To conclude, FAM134B promoter methylation plays a key role in regulating FAM134B expression in-vitro and in-vivo, which in turn contributes to the prediction of the biological aggressiveness of colorectal adenocarcinomas. Furthermore, FAM134B methylation might act as a marker in predicting clinical prognosis in patients with colorectal adenocarcinomas. This article is protected by copyright. All rights reserved.
Keyword FAM134B
JK1
Clinical
Colorectal carcinoma
Methylation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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School of Biomedical Sciences Publications
 
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Created: Wed, 17 Jan 2018, 12:16:13 EST