Ferlay, J. et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136, E359–E386 (2015).
Theuer, C. P., Kurosaki, T., Ziogas, A., Butler, J. & Anton-Culver, H. Asian patients with gastric carcinoma in the United States exhibit unique clinical features and superior overall and cancer specific survival rates. Cancer 89, 1883–1892 (2000).
Nashimoto, A. et al. Gastric cancer treated in 2002 in Japan: 2009 annual report of the JGCA nationwide registry. Gastric Cancer 16, 1–27 (2013).
Russo, A., Li, P. & Strong, V. E. Differences in the multimodal treatment of gastric cancer: East versus West. J. Surg. Oncol. http://dx.doi.org/10.1002/jso.24517 (2017).
Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer 20, 1–19 (2017).
Sugano, K. Screening of gastric cancer in Asia. Best Pract. Res. Clin. Gastroenterol. 29, 895–905 (2015).
Dikken, J. L. et al. Treatment of resectable gastric cancer. Therap. Adv. Gastroenterol. 5, 49–69 (2012).
Leung, W. K. et al. Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol. 9, 279–287 (2008).
Vogelaar, I. P. et al. Familial gastric cancer: detection of a hereditary cause helps to understand its etiology. Hered. Cancer Clin. Pract. 10, 18 (2012).
Tan, P. & Yeoh, K. G. Genetics and molecular pathogenesis of gastric adenocarcinoma. Gastroenterology 149, 1153–1162.e3 (2015).
Cover, T. L. Helicobacter pylori diversity and gastric cancer risk. mBio 7, e01869-15 (2016).
Forman, D. & Burley, V. J. Gastric cancer: global pattern of the disease and an overview of environmental risk factors. Best Pract. Res. Clin. Gastroenterol. 20, 633–649 (2006).
Karimi, P., Islami, F., Anandasabapathy, S., Freedman, N. D. & Kamangar, F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol. Biomarkers Prev. 23, 700–713 (2014).
Saju, P. et al. Host SHP1 phosphatase antagonizes Helicobacter pylori CagA and can be downregulated by Epstein-Barr virus. Nat. Microbiol. 1, 16026 (2016).
Meimarakis, G. et al. Helicobacter pylori as a prognostic indicator after curative resection of gastric carcinoma: a prospective study. Lancet Oncol. 7, 211–222 (2006).
Yamamoto, Y., Fujisaki, J., Omae, M., Hirasawa, T. & Igarashi, M. Helicobacter pylori-negative gastric cancer: characteristics and endoscopic findings. Dig. Endosc. 27, 551–561 (2015).
Hu, B. et al. Gastric cancer: classification, histology and application of molecular pathology. J. Gastrointest. Oncol. 3, 251–261 (2012).
Lauren, P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol. Microbiol. Scand. 64, 31–49 (1965).
Correa, P. & Piazuelo, M. B. Helicobacter pylori infection and gastric adenocarcinoma. US Gastroenterol. Hepatol. Rev. 7, 59–64 (2011).
Takenaka, R. et al. Helicobacter pylori eradication reduced the incidence of gastric cancer, especially of the intestinal type. Aliment. Pharmacol. Ther. 25, 805–812 (2007).
Bang, Y. J. et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376, 687–697 (2010).
Yamamoto, H. et al. An updated review of gastric cancer in the next-generation sequencing era: insights from bench to bedside and vice versa. World J. Gastroenterol. 20, 3927–3937 (2014).
Lin, Y., Wu, Z., Guo, W. & Li, J. Gene mutations in gastric cancer: a review of recent next-generation sequencing studies. Tumour Biol. 36, 7385–7394 (2015).
Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513, 202–209 (2014).
Cristescu, R. et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat. Med. 21, 449–456 (2015).
Chang, M. S. et al. CpG island methylation status in gastric carcinoma with and without infection of Epstein-Barr virus. Clin. Cancer Res. 12, 2995–3002 (2006).
Yoda, Y. et al. Integrated analysis of cancer-related pathways affected by genetic and epigenetic alterations in gastric cancer. Gastric Cancer 18, 65–76 (2015).
Feinberg, A. P. & Tycko, B. The history of cancer epigenetics. Nat. Rev. Cancer 4, 143–153 (2004).
Ito, S. et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333, 1300–1303 (2011).
Pastor, W. A., Aravind, L. & Rao, A. TETonic shift: biological roles of TET proteins in DNA demethylation and transcription. Nat. Rev. Mol. Cell Biol. 14, 341–356 (2013).
Yang, Q. et al. Decreased 5-hydroxymethylcytosine (5-hmC) is an independent poor prognostic factor in gastric cancer patients. J. Biomed. Nanotechnol. 9, 1607–1616 (2013).
Patil, V., Ward, R. L. & Hesson, L. B. The evidence for functional non-CpG methylation in mammalian cells. Epigenetics 9, 823–828 (2014).
Rando, O. J. Combinatorial complexity in chromatin structure and function: revisiting the histone code. Curr. Opin. Genet. Dev. 22, 148–155 (2012).
Jiang, C. & Pugh, B. F. Nucleosome positioning and gene regulation: advances through genomics. Nat. Rev. Genet. 10, 161–172 (2009).
Saletore, Y. et al. The birth of the epitranscriptome: deciphering the function of RNA modifications. Genome Biol. 13, 175 (2012).
Yue, Y., Liu, J. & He, C. RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation. Genes Dev. 29, 1343–1355 (2015).
McGuinness, D. H. & McGuinness, D. m6a RNA methylation: the implications for health and disease. J. Cancer Sci. Clin. Oncol. 1, 105 (2014).
Han, L. et al. The genomic landscape and clinical relevance of A-to-I RNA editing in human cancers. Cancer Cell 28, 515–528 (2015).
Wang, I. X. et al. ADAR regulates RNA editing, transcript stability, and gene expression. Cell Rep. 5, 849–860 (2013).
Chan, T. H. et al. ADAR-mediated RNA editing predicts progression and prognosis of gastric cancer. Gastroenterology 151, 637–650 (2016).
Huang, Y. K. & Yu, J. C. Circulating microRNAs and long non-coding RNAs in gastric cancer diagnosis: an update and review. World J. Gastroenterol. 21, 9863–9886 (2015).
Tsai, M. M. et al. Potential diagnostic, prognostic and therapeutic targets of microRNAs in human gastric cancer. Int. J. Mol. Sci. 17, E945 (2016).
Wang, J. et al. Long noncoding RNAs in gastric cancer: functions and clinical applications. Onco Targets Ther. 9, 681–697 (2016).
Petrocca, F. et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 13, 272–286 (2008).
Kim, Y. K. et al. Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer. Nucleic Acids Res. 37, 1672–1681 (2009).
Xia, L. et al. miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int. J. Cancer 123, 372–379 (2008).
Wang, F. et al. MicroRNA-19a/b regulates multidrug resistance in human gastric cancer cells by targeting PTEN. Biochem. Biophys. Res. Commun. 434, 688–694 (2013).
Zhu, W. et al. miR-497 modulates multidrug resistance of human cancer cell lines by targeting BCL2. Med. Oncol. 29, 384–391 (2012).
Shang, Y. et al. miR-508-5p regulates multidrug resistance of gastric cancer by targeting ABCB1 and ZNRD1. Oncogene 33, 3267–3276 (2014).
Zhang, Y., Lu, Q. & Cai, X. MicroRNA-106a induces multidrug resistance in gastric cancer by targeting RUNX3. FEBS Lett. 587, 3069–3075 (2013).
Wang, P. et al. MicroRNA-126 increases chemosensitivity in drug-resistant gastric cancer cells by targeting EZH2. Biochem. Biophys. Res. Commun. 479, 91–96 (2016).
Lu, C., Shan, Z., Li, C. & Yang, L. MiR-129 regulates cisplatin-resistance in human gastric cancer cells by targeting P-gp. Biomed. Pharmacother. 86, 450–456 (2017).
Ueda, T. et al. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 11, 136–146 (2010).
Yepes, S. et al. Co-expressed miRNAs in gastric adenocarcinoma. Genomics 108, 93–101 (2016).
Yin, H. et al. DNA methylation mediated down-regulating of microRNA-33b and its role in gastric cancer. Sci. Rep. 6, 18824 (2016).
Suzuki, H., Maruyama, R., Yamamoto, E. & Kai, M. DNA methylation and microRNA dysregulation in cancer. Mol. Oncol. 6, 567–578 (2012).
da Silva Oliveira, K. C. et al. Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer. World J. Gastroenterol. 22, 7951–7962 (2016).
Li, T., Mo, X., Fu, L., Xiao, B. & Guo, J. Molecular mechanisms of long noncoding RNAs on gastric cancer. Oncotarget 7, 8601–8612 (2016).
Endo, H. et al. Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. PLoS ONE 8, e77070 (2013).
Liu, X. H. et al. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol. Cancer 13, 92 (2014).
Xia, T. et al. Long noncoding RNA associated-competing endogenous RNAs in gastric cancer. Sci. Rep. 4, 6088 (2014).
Chen, L. L. The biogenesis and emerging roles of circular RNAs. Nat. Rev. Mol. Cell Biol. 17, 205–211 (2016).
Chen, J. et al. Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer. Cancer Lett. 388, 208–219 (2016).
Oue, N. et al. DNA methylation of multiple genes in gastric carcinoma: association with histological type and CpG island methylator phenotype. Cancer Sci. 94, 901–905 (2003).
Kim, J. H., Jung, E. J., Lee, H. S., Kim, M. A. & Kim, W. H. Comparative analysis of DNA methylation between primary and metastatic gastric carcinoma. Oncol. Rep. 21, 1251–1259 (2009).
Kupcinskaite-Noreikiene, R. et al. Gene methylation profile of gastric cancerous tissue according to tumor site in the stomach. BMC Cancer 16, 40 (2016).
Li, Y., Liang, J. & Hou, P. Hypermethylation in gastric cancer. Clin. Chim. Acta 448, 124–132 (2015).
Shimazu, T. et al. Association of gastric cancer risk factors with DNA methylation levels in gastric mucosa of healthy Japanese: a cross-sectional study. Carcinogenesis 36, 1291–1298 (2015).
Maekita, T. et al. High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin. Cancer Res. 12, 989–995 (2006).
Yoshida, T. et al. Alu and Satα hypomethylation in Helicobacter pylori-infected gastric mucosae. Int. J. Cancer 128, 33–39 (2011).
Chan, A. O. et al. Eradication of Helicobacter pylori infection reverses E-cadherin promoter hypermethylation. Gut 55, 463–468 (2006).
Sepulveda, A. R. et al. CpG methylation and reduced expression of O6-methylguanine DNA methyltransferase is associated with Helicobacter pylori infection. Gastroenterology 138, 1836–1844 (2010).
Perri, F. et al. Aberrant DNA methylation in non-neoplastic gastric mucosa of H. Pylori infected patients and effect of eradication. Am. J. Gastroenterol. 102, 1361–1371 (2007).
Leung, W. K. et al. Effects of Helicobacter pylori eradication on methylation status of E-cadherin gene in noncancerous stomach. Clin. Cancer Res. 12, 3216–3221 (2006).
Niwa, T. et al. Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells. Cancer Res. 70, 1430–1440 (2010).
Hur, K. et al. Insufficient role of cell proliferation in aberrant DNA methylation induction and involvement of specific types of inflammation. Carcinogenesis 32, 35–41 (2011).
Matsusaka, K. et al. Classification of Epstein-Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes. Cancer Res. 71, 7187–7197 (2011).
Namba-Fukuyo, H. et al. TET2 functions as a resistance factor against DNA methylation acquisition during Epstein-Barr virus infection. Oncotarget 7, 81512–81526 (2016).
Hino, R. et al. Activation of DNA methyltransferase 1 by EBV latent membrane protein 2A leads to promoter hypermethylation of PTEN gene in gastric carcinoma. Cancer Res. 69, 2766–2774 (2009).
Kusano, M. et al. Genetic, epigenetic, and clinicopathologic features of gastric carcinomas with the CpG island methylator phenotype and an association with Epstein-Barr virus. Cancer 106, 1467–1479 (2006).
Wang, K. et al. Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nat. Genet. 43, 1219–1223 (2011).
He, L. J. et al. Prognostic significance of overexpression of EZH2 and H3k27me3 proteins in gastric cancer. Asian Pac. J. Cancer Prev. 13, 3173–3178 (2012).
Etoh, T. et al. Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers. Am. J. Pathol. 164, 689–699 (2004).
Nishikawaji, T. et al. Oncogenic roles of the SETDB2 histone methyltransferase in gastric cancer. Oncotarget 7, 67251–67265 (2016).
Park, J. L. et al. Decrease of 5hmC in gastric cancers is associated with TET1 silencing due to with DNA methylation and bivalent histone marks at TET1 CpG island 3<0x0374>-shore. Oncotarget 6, 37647–37662 (2015).
Xu, W. et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 19, 17–30 (2011).
Chou, N. H. et al. Isocitrate dehydrogenase 2 dysfunction contributes to 5-hydroxymethylcytosine depletion in gastric cancer cells. Anticancer Res. 36, 3983–3990 (2016).
Laukka, T. et al. Fumarate and succinate regulate expression of hypoxia-inducible genes via TET enzymes. J. Biol. Chem. 291, 4256–4265 (2016).
Chan, A. W., Gill, R. S., Schiller, D. & Sawyer, M. B. Potential role of metabolomics in diagnosis and surveillance of gastric cancer. World J. Gastroenterol. 20, 12874–12882 (2014).
Thienpont, B. et al. Tumour hypoxia causes DNA hypermethylation by reducing TET activity. Nature 537, 63–68 (2016).
Park, J. H. et al. Identification of DNA methylation changes associated with human gastric cancer. BMC Med. Genomics 4, 82 (2011).
Choi, I. S. & Wu, T. T. Epigenetic alterations in gastric carcinogenesis. Cell Res. 15, 247–254 (2005).
Xie, C. et al. Melanoma associated antigen (MAGE)-A3 promotes cell proliferation and chemotherapeutic drug resistance in gastric cancer. Cell. Oncol. (Dordr.) 39, 175–186 (2016).
Baek, S. J. et al. Integrated epigenomic analyses of enhancer as well as promoter regions in gastric cancer. Oncotarget 7, 25620–25631 (2016).
Chiurillo, M. A. Role of the Wnt/β-catenin pathway in gastric cancer: an in-depth literature review. World J. Exp. Med. 5, 84–102 (2015).
Lee, J.-H. et al. Frequent CpG island methylation in precursor lesions and early gastric adenocarcinomas. Oncogene 23, 4646–4654 (2004).
To, K. F. et al. Promoter hypermethylation of tumor-related genes in gastric intestinal metaplasia of patients with and without gastric cancer. Int. J. Cancer 102, 623–628 (2002).
Zou, X. P. et al. Promoter hypermethylation of multiple genes in early gastric adenocarcinoma and precancerous lesions. Hum. Pathol. 40, 1534–1542 (2009).
Kang, G. H. et al. CpG island methylation in premalignant stages of gastric carcinoma. Cancer Res. 61, 2847–2851 (2001).
Schneider, B. G. et al. DNA methylation predicts progression of human gastric lesions. Cancer Epidemiol. Biomarkers Prev. 24, 1607–1613 (2015).
Sepulveda, J. L. et al. High-definition CpG methylation of novel genes in gastric carcinogenesis identified by next-generation sequencing. Mod. Pathol. 29, 182–193 (2016).
Nakajima, T. et al. Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers. Cancer Epidemiol. Biomarkers Prev. 15, 2317–2321 (2006).
Lu, Z. & Deng, D. in Current Topics in Gastritis — 2012 Ch. 8 (ed. Mozsik, G.) (2012).
Bae, J. M. et al. ALU and LINE-1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications. Int. J. Cancer 131, 1323–1331 (2012).
Leodolter, A. et al. Somatic DNA hypomethylation in H. pylori-associated high-risk gastritis and gastric cancer: enhanced somatic hypomethylation associates with advanced stage cancer. Clin. Transl Gastroenterol. 6, e85 (2015).
Niwa, T. et al. Prevention of Helicobacter pylori-induced gastric cancers in gerbils by a DNA demethylating agent. Cancer Prev. Res. (Phila.) 6, 263–270 (2013).
Yang, W. et al. Epigenetic silencing of GDF1 disrupts SMAD signaling to reinforce gastric cancer development. Oncogene 35, 2133–2144 (2016).
Hattori, N. & Ushijima, T. Epigenetic impact of infection on carcinogenesis: mechanisms and applications. Genome Med. 8, 10 (2016).
Asada, K. et al. Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study. Gut 64, 388–396 (2015).
Bibikova, M. et al. High density DNA methylation array with single CpG site resolution. Genomics 98, 288–295 (2011).
Yang, X. et al. Gene body methylation can alter gene expression and is a therapeutic target in cancer. Cancer Cell 26, 577–590 (2014).
Zouridis, H. et al. Methylation subtypes and large-scale epigenetic alterations in gastric cancer. Sci Transl Med. 4, 156ra140 (2012).
Huang, Y. et al. The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing. PLoS ONE 5, e8888 (2010).
Stroud, H., Feng, S. H., Kinney, S. M., Pradhan, S. & Jacobsen, S. E. 5-hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells. Genome Biol. 12, R54 (2011).
Johnson, K. C. et al. 5-hydroxymethylcytosine localizes to enhancer elements and is associated with survival in glioblastoma patients. Nat. Commun. 7, 13177 (2016).
Jones, P. A. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13, 484–492 (2012).
Park, Y. S. et al. The global histone modification pattern correlates with cancer recurrence and overall survival in gastric adenocarcinoma. Ann. Surg. Oncol. 15, 1968–1976 (2008).
Takahashi, H. et al. Overexpression of phosphorylated histone H3 is an indicator of poor prognosis in gastric adenocarcinoma patients. Appl. Immunohistochem. Mol. Morphol. 14, 296–302 (2006).
Wu, J., Smith, L. T., Plass, C. & Huang, T. H. ChIP-chip comes of age for genome-wide functional analysis. Cancer Res. 66, 6899–6902 (2006).
Muratani, M. et al. Nanoscale chromatin profiling of gastric adenocarcinoma reveals cancer-associated cryptic promoters and somatically acquired regulatory elements. Nat. Commun. 5, 4361 (2014).
Zhang, L., Zhong, K., Dai, Y. & Zhou, H. Genome-wide analysis of histone H3 lysine 27 trimethylation by ChIP-chip in gastric cancer patients. J. Gastroenterol. 44, 305–312 (2009).
Qamra, A. et al. Epigenomic promoter alterations amplify gene isoform and immunogenic diversity in gastric adenocarcinoma. Cancer Discov. http://dx.doi.org/10.1158/2159-8290.CD-16-1022 (2017).
Ooi, W. F. et al. Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity. Nat. Commun. 7, 12983 (2016).
Rose, N. R. & Klose, R. J. Understanding the relationship between DNA methylation and histone lysine methylation. Biochim. Biophys. Acta 1839, 1362–1372 (2014).
Vire, E. et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439, 871–874 (2006).
Ning, X. et al. DNMT1 and EZH2 mediated methylation silences the microRNA-200b/a/429 gene and promotes tumor progression. Cancer Lett. 359, 198–205 (2015).
Gao, F. et al. Direct ChIP-bisulfite sequencing reveals a role of H3K27me3 mediating aberrant hypermethylation of promoter CpG islands in cancer cells. Genomics 103, 204–210 (2014).
Meng, C. F., Zhu, X. J., Peng, G. & Dai, D. Q. Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines. World J. Gastroenterol. 13, 6166–6171 (2007).
Toiyama, Y., Okugawa, Y. & Goel, A. DNA methylation and microRNA biomarkers for noninvasive detection of gastric and colorectal cancer. Biochem. Biophys. Res. Commun. 455, 43–57 (2014).
Warton, K., Mahon, K. L. & Samimi, G. Methylated circulating tumor DNA in blood: power in cancer prognosis and response. Endocr. Relat. Cancer 23, R157–R171 (2016).
Watanabe, Y. et al. Sensitive and specific detection of early gastric cancer using DNA methylation analysis of gastric washes. Gastroenterology 136, 2149–2158 (2009).
Sapari, N. S., Loh, M., Vaithilingam, A. & Soong, R. Clinical potential of DNA methylation in gastric cancer: a meta-analysis. PLoS ONE 7, e36275 (2012).
Shin, D. G. et al. A methylation profile of circulating cell free DNA for the early detection of gastric cancer and the effects after surgical resection. J. Clin. Exp. Oncol. 5, 1 (2016).
Maeda, M. et al. High impact of methylation accumulation on metachronous gastric cancer: 5-year follow-up of a multicentre prospective cohort study. Gut http://dx.doi.org/10.1136/gutjnl-2016-313387 (2016).
Nervi, C., De Marinis, E. & Codacci-Pisanelli, G. Epigenetic treatment of solid tumours: a review of clinical trials. Clin. Epigenetics 7, 127 (2015).
Nakamura, M. et al. Decitabine inhibits tumor cell proliferation and up-regulates E-cadherin expression in Epstein-Barr virus-associated gastric cancer. J. Med. Virol. 89, 508–517 (2017).
Chen, J. et al. BET inhibition attenuates Helicobacter pylori-induced inflammatory response by suppressing inflammatory gene transcription and enhancer activation. J. Immunol. 196, 4132–4142 (2016).
Montenegro, R. C. et al. BET inhibition as a new strategy for the treatment of gastric cancer. Oncotarget 7, 43997–44012 (2016).
Abdelfatah, E., Kerner, Z., Nanda, N. & Ahuja, N. Epigenetic therapy in gastrointestinal cancer: the right combination. Therap. Adv. Gastroenterol. 9, 560–579 (2016).
Chiappinelli, K. B. et al. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162, 974–986 (2015).
Covre, A. et al. Antitumor activity of epigenetic immunomodulation combined with CTLA-4 blockade in syngeneic mouse models. Oncoimmunology 4, e1019978 (2015).
Li, H. et al. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget 5, 587–598 (2014).
Moehler, M. et al. Immunotherapy in gastrointestinal cancer: recent results, current studies and future perspectives. Eur. J. Cancer 59, 160–170 (2016).
Muro, K. et al. LBA15A phase 1B study of pembrolizumab (PEMBRO; MK-3475) in patients (PTS) with advanced gastric cancer [abstract]. Ann. Oncol. 25, LBA15 (2014).
Mazor, T., Pankov, A., Song, J. S. & Costello, J. F. Intratumoral heterogeneity of the epigenome. Cancer Cell 29, 440–451 (2016).
Hou, Y. et al. Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas. Cell Res. 26, 304–319 (2016).
The Cancer Genome Atlas. Comprehensive molecular characterization of gastric adenocarcinoma. https://tcga-data.nci.nih.gov/docs/publications/stad_2014/ (2014)
Loh, M. et al. DNA methylation subgroups and the CpG island methylator phenotype in gastric cancer: a comprehensive profiling approach. BMC Gastroenterology 14, 55 (2014).
Chong, Y. et al. DNA methylation status of a distinctively different subset of genes is associated with each histologic Lauren classification subtype in early gastric carcinogenesis. Oncol. Rep. 31, 2535–2544 (2014).
Kim, J. G. et al. Comprehensive DNA methylation and extensive mutation analyses reveal an association between the CpG island methylator phenotype and oncogenic mutations in gastric cancers. Cancer Lett. 330, 33–40 (2013).
Kang, G. H. et al. DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis. Lab. Invest. 88, 161–170 (2008).
Bernal, C. et al. Reprimo as a potential biomarker for early detection in gastric cancer. Clin. Cancer Res. 14, 6264–6269 (2008).
Ng, E. K. et al. Quantitative analysis and diagnostic significance of methylated SLC19A3 DNA in the plasma of breast and gastric cancer patients. PLoS ONE 6, e22233 (2011).
Guo, W. et al. Aberrant methylation of the CpG island of HLTF gene in gastric cardia adenocarcinoma and dysplasia. Clin. Biochem. 44, 784–788 (2011).
Chen, X., Lin, Z., Xue, M., Si, J. & Chen, S. Zic1 promoter hypermethylation in plasma DNA is a potential biomarker for gastric cancer and intraepithelial neoplasia. PLoS ONE 10, e0133906 (2015).
Zhang, X. et al. Detection of aberrant promoter methylation of RNF180, DAPK1 and SFRP2 in plasma DNA of patients with gastric cancer. Oncol. Lett. 8, 1745–1750 (2014).
Yang, Q. et al. Promoter hypermethylation of BCL6B gene is a potential plasma DNA biomarker for gastric cancer. Biomarkers 18, 721–725 (2013).
Pimson, C. et al. Aberrant methylation of PCDH10 and RASSF1A genes in blood samples for non-invasive diagnosis and prognostic assessment of gastric cancer. PeerJ 4, e2112 (2016).
Sakakura, C. et al. Quantitative analysis of tumor-derived methylated RUNX3 sequences in the serum of gastric cancer patients. Anticancer Res. 29, 2619–2625 (2009).
Wang, Y. C. et al. Detection of RASSF1A promoter hypermethylation in serum from gastric and colorectal adenocarcinoma patients. World J. Gastroenterol. 14, 3074–3080 (2008).
Balgkouranidou, I. et al. Prognostic role of APC and RASSF1A promoter methylation status in cell free circulating DNA of operable gastric cancer patients. Mutat. Res. 778, 46–51 (2015).
Leung, W. K. et al. Potential diagnostic and prognostic values of detecting promoter hypermethylation in the serum of patients with gastric cancer. Br. J. Cancer 92, 2190–2194 (2005).
Lee, T. L. et al. Detection of gene promoter hypermethylation in the tumor and serum of patients with gastric carcinoma. Clin. Cancer Res. 8, 1761–1766 (2002).
Balgkouranidou, I. et al. Assessment of SOX17 DNA methylation in cell free DNA from patients with operable gastric cancer. Association with prognostic variables and survival. Clin. Chem. Lab. Med. 51, 1505–1510 (2013).
Ling, Z. Q. et al. Circulating methylated XAF1 DNA indicates poor prognosis for gastric cancer. PLoS ONE 8, e67195 (2013).
Li, W. H. et al. Detection of OSR2, VAV3, and PPFIA3 methylation in the serum of patients with gastric cancer. Dis. Markers 2016, 5780538 (2016).
Kolesnikova, E. V. et al. Circulating DNA in the blood of gastric cancer patients. Ann. NY Acad. Sci. 1137, 226–231 (2008).
Yu, J. L. et al. Methylated TIMP-3 DNA in body fluids is an independent prognostic factor for gastric cancer. Arch. Pathol. Lab. Med. 138, 1466–1473 (2014).
Ikoma, H. et al. Correlation between serum DNA methylation and prognosis in gastric cancer patients. Anticancer Res. 26, 2313–2316 (2006).
Han, J. et al. Circulating methylated MINT2 promoter DNA is a potential poor prognostic factor in gastric cancer. Dig. Dis. Sci. 59, 1160–1168 (2014).
Cheng, L. L. et al. TP53 genomic status regulates sensitivity of gastric cancer cells to the histone methylation inhibitor 3-deazaneplanocin A (DZNep). Clin. Cancer Res. 18, 4201–4212 (2012).
Chen, Y. T. et al. The novel EZH2 inhibitor, GSK126, suppresses cell migration and angiogenesis via down-regulating VEGF-A. Cancer Chemother. Pharmacol. 77, 757–765 (2016).
Chang, H. et al. Identification of genes related to a synergistic effect of taxane and suberoylanilide hydroxamic acid combination treatment in gastric cancer cells. J. Cancer Res. Clin. Oncol. 136, 1901–1913 (2010).
Hibino, S. et al. Inhibitors of enhancer of zeste homolog 2 (EZH2) activate tumor-suppressor microRNAs in human cancer cells. Oncogenesis 3, e104 (2014).
Yansong, Z. Genomic analysis of chemo-resistance to HDAC inhibitor in gastric cancer cells [Thesis, National University of Singapore]. ScholarBank http://scholarbank.nus.sg/handle/10635/49396 (2013).
Zhang, X., Yashiro, M., Ren, J. & Hirakawa, K. Histone deacetylase inhibitor, trichostatin A, increases the chemosensitivity of anticancer drugs in gastric cancer cell lines. Oncol. Rep. 16, 563–568 (2006).
Regel, I. et al. Pan-histone deacetylase inhibitor panobinostat sensitizes gastric cancer cells to anthracyclines via induction of CITED2. Gastroenterology 143, 99–109.e10 (2012).
Zheng, Y. C. et al. Triazole-dithiocarbamate based selective lysine specific demethylase 1 (LSD1) inactivators inhibit gastric cancer cell growth, invasion, and migration. J. Med. Chem. 56, 8543–8560 (2013).
Cai, X. Z. et al. Curcumin suppresses proliferation and invasion in human gastric cancer cells by downregulation of PAK1 activity and cyclin D1 expression. Cancer Biol. Ther. 8, 1360–1368 (2009).
Liu, X. et al. Curcumin inhibits proliferation of gastric cancer cells by impairing ATP-sensitive potassium channel opening. World J. Surg. Oncol. 12, 389 (2014).
Hirai, S. et al. Antitumor effects of a sirtuin inhibitor, tenovin-6, against gastric cancer cells via death receptor 5 up-regulation. PLoS ONE 9, e102831 (2014).
Fetterly, G. J. et al. A phase I pharmacokinetic (PK) study of vorinostat (V) in combination with irinotecan (I), 5-fluorouracil (5FU), and leucovorin (FOLFIRI) in advanced upper gastrointestinal cancers (AGC) [abstract]. J. Clin. Oncol. 27 (Suppl.), e15540 (2009).
Yoo, C. et al. Phase I and pharmacodynamic study of vorinostat combined with capecitabine and cisplatin as first-line chemotherapy in advanced gastric cancer. Invest. New Drugs 32, 271–278 (2014).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01045538 (2016).
Yoo, C. et al. Vorinostat in combination with capecitabine plus cisplatin as a first-line chemotherapy for patients with metastatic or unresectable gastric cancer: phase II study and biomarker analysis. Br. J. Cancer 114, 1185–1190 (2016).
Schneider, B. J. et al. Phase I study of epigenetic priming with azacitidine prior to standard neoadjuvant chemotherapy for patients with resectable gastric and esophageal adenocarcinoma. Clin. Cancer Res. http://dx.doi.org/10.1158/1078-0432.CCR-16-1896 (2016).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02900651 (2017).