nach oben

International Journal of Clinical Oncology

Erschienen in:

21.03.2020 | Original Article

SAMD14 promoter methylation is strongly associated with gene expression and poor prognosis in gastric cancer

verfasst von: Xiaoyang Xu, Xiaojing Chang, Yan Xu, Peng Deng, Jiang Wang, Chundong Zhang, Xinjiang Zhu, Shuchen Chen, Dongqiu Dai

Erschienen in: International Journal of Clinical Oncology | Ausgabe 6/2020

Einloggen, um Zugang zu erhalten

Abstract

Background

Gastric cancer (GC) is the fifth most common malignancy worldwide and the third leading cause of cancer-related mortality. In recent years, SAMD14 has been studied in various malignant cancers; however, little is known about the exact mechanisms of SAMD14 involvement in carcinogenesis and malignant progression.

Methods

60 paired GC-normal gastric tissues were evaluated for their SAMD14 mRNA expression in relation to SAMD14 gene promoter methylation. GC patient survival was assessed by Kaplan–Meier analyses and a Cox’s proportional hazard model was employed for multivariate analyses.

Results

SAMD14 expression was significantly inversely correlated with the Borrmann type (P = 0.017), lymph node metastasis (P = 0.006) and tumor-node-metastasis (TNM) stage (P = 0.033). Methylation-specific PCR (MSP) revealed hyper-methylation of the SAMD14 promoter in 56.7% (34/60) of the primary GC tissues tested and in 10% (6/60) of matched non-malignant tissues. The SAMD14 promoter methylation status was also related to pathological differentiation, Borrmann type, TNM stage and lymph node metastasis. The results showed SAMD14 expression was significantly downregulated in Borrmann type, lymph node metastasis and TNM stage, which showed significantly higher methylation. SAMD14 promoter hyper-methylation was significantly associated with a poor prognosis and could serve as an independent marker for survival using multivariate Cox regression analysis.

Conclusions

Our results indicated that promoter methylation was a key mechanism contributing to the downregulation of SAMD14 in GC. SAMD14 may be an epigenetically silenced tumor suppressor gene, and hyper-methylation of the SAMD14 promoter may serve as a biomarker to predict the clinical outcome of GC.

Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424CrossRef

Fock KM (2010) Review article: the epidemiology and prevention of gastric cancer. Aliment Pharmacol Ther 40:250–260CrossRef

Wang K, Ren Y, Ma Z et al (2019) Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) as preoperative and postoperativechemotherapy compared with surgery followed by chemotherapy for patients with locallyadvanced gastric cancer: a propensity score-based analysis. Cancer Manag Res 10(11):3009–3020CrossRef

Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128:683–692CrossRefPubMedPubMedCentral

Esteller M (2008) Epigenetics in cancer. N Engl J Med 358:1148–1159CrossRefPubMed

Qu Y, Dang S, Hou P (2013) Gene methylation in gastric cancer. Clin Chim Acta 424:53–65CrossRefPubMed

Yang Z, Li DM, Xie Q et al (2015) Protein expression and promoter methylation of the candidate biomarker TCF21 in gastric cancer. J Cancer Res Clin Oncol 141:211–220CrossRefPubMed

Yu Y, Yan W, Liu X et al (2014) DACT2 is frequently methylated in human gastric cancer and methylation of DACT2 activated Wnt signaling. Am J Cancer Res 4:710–724PubMedPubMedCentral

Ushijima T, Nakajima T, Maekita T (2006) DNA methylation as a marker for the past and future. J Gastroenterol 41:401–407CrossRefPubMed

10.

Li M, He Z, Tong X et al (2018) Detecting rare mutations with heterogeneous effects using a family-based genetic random field method. Genetics 210(2):463–476CrossRefPubMedPubMedCentral

11.

Sun W, Iijima T, Kano J et al (2008) Frequent aberrant methylation of the promoter region of sterile alpha motif domain 14 in pulmonary adenocarcinoma. Cancer Sci 99(11):2177–2184CrossRefPubMed

12.

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408CrossRefPubMed

13.

Li LC, Dahiya R (2002) MethPrimer: designing primers for methylation PCRs. Bioinformatics 18(11):1427–1431CrossRefPubMed

14.

Ferlay J, Soerjomataram I, Dikshit R et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386CrossRefPubMed

15.

Fitzmaurice C, Allen C, Barber RM, Global burden of disease cancer collaboration et al (2017) Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol 3(4):524–548CrossRefPubMed

16.

Hewitt KJ, Kim DH, Devadas P et al (2015) Hematopoietic Signaling mechanism revealed from a stem/progenitor cell cistrome. Mol Cell 59(1):62–74CrossRefPubMedPubMedCentral

17.

Fehrmann RS, Jansen RC, Veldink JH et al (2011) Trans-eQTLs reveal that independent genetic variants associated with a complex phenotype converge on intermediate genes, with a major role for the HLA. PLoS Genet 7:e1002197CrossRefPubMedPubMedCentral

18.

Thurner L, Preuss KD, Bewarder M et al (2018) Hyper-N-glycosylated SAMD14 and neurabin-I as driver autoantigens of primary central nervous system lymphoma. Blood 132(26):2744–2753CrossRefPubMed

19.

Mali RS, Ma P, Zeng LF et al (2012) Role of SHP2 phosphatase in KIT-induced transformation: Identification of SHP2 as a druggable target in diseases involving oncogenic KIT. Blood 120:2669–2678CrossRefPubMedPubMedCentral

20.

Shen Y, Takahashi M, Byun HM et al (2012) Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells. Cancer Biol Ther 13(7):542–552CrossRefPubMedPubMedCentral

21.

Ushijima T (2005) Detection and interpretation of altered methylation patterns in cancer cells. Nat Rev Cancer 5:223–231CrossRefPubMed

22.

Fang WL, Chen MH, Huang KH et al (2019) Analysis of the clinical significance of DNA methylation in gastric cancer based on a genome-wide high-resolution array. Clin Epigenetics 11:154CrossRefPubMedPubMedCentral

23.

Wu J, Xiao Y, Xia C et al (2017) Identification of biomarkers for predicting lymph node metastasis of stomach cancer using clinical DNA methylation data. Dis Markers 2017:5745724PubMedPubMedCentral

24.

Ushiku H, Yamashita K, Ema A et al (2017) DNA diagnosis of peritoneal fluid cytology test by CDO1 promoter DNA hypermethylation in gastric cancer. Gastric Cancer 20(5):784–792CrossRefPubMed

Titel: SAMD14 promoter methylation is strongly associated with gene expression and poor prognosis in gastric cancer
verfasst von: Xiaoyang Xu
Xiaojing Chang
Yan Xu
Peng Deng
Jiang Wang
Chundong Zhang
Xinjiang Zhu
Shuchen Chen
Dongqiu Dai
Publikationsdatum: 21.03.2020
Verlag: Springer Singapore
Erschienen in: International Journal of Clinical Oncology / Ausgabe 6/2020
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-020-01647-4

Springer Medizin

SAMD14 promoter methylation is strongly associated with gene expression and poor prognosis in gastric cancer