Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 3/2016

01-03-2016 | Research Article

Methylation of ASC/TMS1 promoter is associated with poor prognosis of patients with gastric cancer

Authors: L. Wu, C. Zhang, X. Wang, X. Ding, J. Deng, H. Liang

Published in: Clinical and Translational Oncology | Issue 3/2016

Login to get access

Abstract

Objective

This study was conducted to explore the prognostic value of the methylation status of the ASC/TMS1 (apoptosis-associated speck-like protein containing a CARD/the target of methylation-induced silencing-1) promoter in gastric cancer (GC).

Methods

ASC/TMS1 expression was detected in GC tissues and normal gastric mucosal tissues by real-time quantitative PCR and Western blot analysis. Methylation-specific PCR (MSP) analysis was performed to detect the methylated degrees of the DNA of the ASC/TMS1 promoter of 200 GC patients. Associations between molecular, clinicopathological characteristics and survival data were analyzed.

Results

The mRNA and protein expression levels of ASC/TMS1 in GC tissues were lower than those in normal gastric mucosal tissues. With the MSP detection, ASC/TMS1 promoter methylation was found in 68 (34 %) in 200 GC tissues, while none of 40 normal gastric mucosal tissues were found to be methylated. The size of primary tumor and lymph node metastasis were identified as independent relative factors of methylation status of the ASC/TMS1 promoter in GC tissues. Multivariate analysis results demonstrated that the degree of differentiation, serosal invasion, lymph node metastasis and methylated status of ASC/TMS1 promoter were independent prognostic indicators of GC. Lymph node metastasis and methylated status of ASC/TMS1 promoter were optimal prognostic predictors of GC patients, as identified by Cox regression with Akaike information criterion value calculation.

Conclusions

The methylated status of ASC/TMS1 promoter had the potential applicability for clinical evaluation the prognosis of GC.
Literature
1.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.CrossRefPubMed
2.
3.
Deng J, Liang H, Ying G, Zhang R, Wang B, Yu J, et al. Methylation of CpG sites in RNF180 DNA promoter prediction poor survival of gastric cancer. Oncotarget. 2014;5:3173–83.PubMedCentralCrossRefPubMed
4.
Laird PW, Jaenisch R. The role of DNA methylation in cancer genetic and epigenetics. Annu Rev Genet. 1996;30:441–64.CrossRefPubMed
5.
Masumoto J, Taniguchi S, Ayukawa K, Sarvotham H, Kishino T, Niikawa N, et al. ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells. J Biol Chem. 1999;274:33835–8.CrossRefPubMed
6.
7.
Conway KE, McConnell BB, Bowring CE, Donald CD, Warren ST. Vertino PM TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers. Cancer Res. 2000;60:6236–42.PubMed
8.
Virmani A, Rathi A, Sugio K, Sathyanarayana UG, Toyooka S, Kischel FC, et al. Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast cancer. Int J Cancer. 2003;106:198–204.CrossRefPubMed
9.
Collard RL, Harya NS, Monzon FA, Maier CE, O’Keefe DS. Methylation of the ASC gene promoter is associated with aggressive prostate cancer. Prostate. 2006;66:687–95.CrossRefPubMed
10.
Grau E, Martinez F, Orellana C, Canete A, Yanez Y, Oltra S, et al. Hypermethylation of apoptotic genes as independent prognostic factor in neuroblastoma disease. Mol Carcinog. 2001;50:153–62.CrossRef
11.
Stone AR, Bobo W, Brat DJ, Devi NS, Van Meir EG, Vertino PM. Aberrant methylation and down-regulation of TMS1/ASC in human glioblastoma. Am J Pathol. 2004;165:1151–61.PubMedCentralCrossRefPubMed
12.
Deng J, Liang H, Zhang R, Dong Q, Hou Y, Yu J, et al. Applicability of the methylated CpG sites of paired box 5 (PAX5) promoter for prediction the prognosis of gastric cancer. Oncotarget. 2014;5:7420–30.PubMedCentralCrossRefPubMed
13.
14.
Liu W, Luo Y, Dunn JH, Norris DA, Dinarello CA, Fujita M. Dual role of apoptosis-associated speck-like protein containing a CARD (ASC) in tumorigenesis of human melanoma. J Invest Dermatol. 2013;133:518–27.PubMedCentralCrossRefPubMed
15.
Hasegawa M, Kawase K, Inohara N, Imamura R, Yeh WC, Kinoshita T, et al. Mechanism of ASC-mediated apoptosis: biddependent apoptosis in type II cells. Oncogene. 2007;26:1748–56.CrossRefPubMed
16.
Masumoto J, Dowds TA, Schaner P, Chen FF, Ogura Y, Li M, et al. ASC is an activating adaptor for NF-κB and caspase-8-dependent apoptosis. Biochem Biophys Res Commun. 2003;303:69–73.CrossRefPubMed
17.
Stimson KM, Vertino PM. Methylation-mediated silencing of TMS1/ASC is accompanied by histone hypoacetylation and CpG island-localized changes in chromatin architecture. J Biol Chem. 2002;277:4951–8.CrossRefPubMed
18.
Kato K, Iida S, Uetake H, Takagi Y, Yamashita T, Inokuchi M, et al. Methylated TMS1 and DAPK genes predict prognosis and response to chemotherapy in gastric cancer. Int J Cancer. 2008;122:603–8.CrossRefPubMed
19.
Moriai R, Tsuji N, Kobayashi D, Yagihashi A, Namiki Y, Takahashi H, et al. A proapoptotic caspase recruitment domain protein gene, TMS1, is hypermethylated in human breast and gastric cancers. Anticancer Res. 2002;22:4163–8.PubMed
20.
Machida EO, Brock MV, Hooker CM, Nakayama J, Ishida A, Amano J, et al. Hypermethylation of ASC/TMS1 is a sputum marker for late-stage lung cancer. Cancer Res. 2006;66:6210–8.CrossRefPubMed
21.
Zhang Z, Tan S, Zhang L. Prognostic value of apoptosis-associated speck-like protein containing a CARD gene promoter methylation in resectable non-small-cell lung cancer. Clin Lung Cancer. 2006;8:62–5.CrossRefPubMed
22.
Terasawa K, Sagae S, Toyota M, Tsukada K, Ogi K, Satoh A, et al. Epigenetic inactivation of TMS1/ASC in ovarian cancer. Clin Cancer Res. 2004;10:2000–6.CrossRefPubMed
Metadata
Title
Methylation of ASC/TMS1 promoter is associated with poor prognosis of patients with gastric cancer
Authors
L. Wu
C. Zhang
X. Wang
X. Ding
J. Deng
H. Liang
Publication date
01-03-2016
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 3/2016
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-015-1367-y

Other articles of this Issue 3/2016

Clinical and Translational Oncology 3/2016 Go to the issue

Research Article

The impact of prostate gland dimension in genitourinary toxicity after definitive prostate cancer treatment with moderate hypofractionation and volumetric modulated arc radiation therapy

Research Article

Stereotactic body radiotherapy (SBRT) for the treatment of inoperable stage I non-small cell lung cancer patients

Research Article

XIAP inhibitor Embelin inhibits bladder cancer survival and invasion in vitro

Research Article

Prognostic value of circulating tumor cells in metastatic breast cancer: a systemic review and meta-analysis

Review Article

The role of human epididymis protein 4 in the diagnosis of epithelial ovarian cancer

Research Article

Decreased expression of MicroRNA-200 family in human breast cancer is associated with lymph node metastasis
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits