Skip to main content
Erschienen 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

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

Erschienen in: Clinical and Translational Oncology | Ausgabe 3/2016

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.CrossRefPubMed
3.
Zurück zum Zitat 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 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.
Zurück zum Zitat Laird PW, Jaenisch R. The role of DNA methylation in cancer genetic and epigenetics. Annu Rev Genet. 1996;30:441–64.CrossRefPubMed Laird PW, Jaenisch R. The role of DNA methylation in cancer genetic and epigenetics. Annu Rev Genet. 1996;30:441–64.CrossRefPubMed
5.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Hengartner MO. The biochemistry of apoptosis. Nature. 2000;6805:770–6.CrossRef Hengartner MO. The biochemistry of apoptosis. Nature. 2000;6805:770–6.CrossRef
14.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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
Metadaten
Titel
Methylation of ASC/TMS1 promoter is associated with poor prognosis of patients with gastric cancer
verfasst von
L. Wu
C. Zhang
X. Wang
X. Ding
J. Deng
H. Liang
Publikationsdatum
01.03.2016
Verlag
Springer Milan
Erschienen in
Clinical and Translational Oncology / Ausgabe 3/2016
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-015-1367-y

Weitere Artikel der Ausgabe 3/2016

Clinical and Translational Oncology 3/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.