{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T12:35:02Z","timestamp":1776861302708,"version":"3.51.2"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Gastric cancer remains a leading cause of cancer-related mortality worldwide and develops through complex interactions between environmental factors, microbial dysbiosis, and host molecular pathways. Although Helicobacter pylori infection is a well-established risk factor, emerging evidence suggests that broader alterations in the gastric microbiome may also contribute to carcinogenesis. However, the associations between gastric cancer-associated microbial taxa and host gene expression profiles remain insufficiently characterized. This study aimed to identify host gene signatures associated with gastric cancer-related microbial taxa through a descriptive analysis integrating microbiome-derived taxa with transcriptome data. Materials and Methods: Microbial taxa associated with gastric cancer were systematically retrieved from the Disbiome database. Taxon set enrichment analysis (TSEA) was performed using the MicrobiomeAnalyst platform to identify host genes associated with gastric cancer-associated taxa. Importantly, TSEA relies on healthy reference data from the Human Microbiome Project and does not establish gastric cancer-specific interactions or causal relationships. Gene expression levels were subsequently evaluated using The Cancer Genome Atlas (TCGA) PanCancer stomach adenocarcinoma (STAD) dataset by comparing tumor and matched normal gastric tissues. Gene interaction network and transcription factor (TF) enrichment analyses were conducted to explore predicted regulatory relationships. Results: Among 64 microbial taxa associated with gastric cancer, 43 were reported as elevated. After removing overlapping taxa across studies, 37 elevated and 21 reduced taxa were retained for analysis. TSEA identified 11 host genes associated with gastric cancer-related microbial taxa. Transcriptomic analysis demonstrated significant downregulation of DPP6 and DLG2, while KDM4D, USP34, and VDR were significantly upregulated in gastric cancer tissues compared with normal controls. Network and TF enrichment analyses revealed predicted co-expression and co-localization patterns among these genes, suggesting their potential involvement in immune-related processes, epigenetic regulation, and cellular organization. Conclusions: This descriptive study identifies distinct host gene expression signatures associated with gastric cancer-associated microbial dysbiosis. This study is purely associative and hypothesis-generating; no causal or mechanistic inferences are made. TSEA used healthy reference data and therefore does not reflect gastric cancer-specific host\u2013microbe interactions. The findings provide a basis for future hypothesis-driven research but require validation in independent cohorts.<\/jats:p>","DOI":"10.3390\/medicina62050799","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:38:14Z","timestamp":1776854294000},"page":"799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Host Gene Signatures Associated with Gastric Cancer\u2013Associated Microbial Taxa: A Descriptive Microbiome\u2013Transcriptome Study"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8534-1781","authenticated-orcid":false,"given":"Ozgur","family":"Albuz","sequence":"first","affiliation":[{"name":"Department of General Surgery, Dr. Abdurrahman Yurtaslan, Ankara Oncology Training and Research Hospital, 06200 Ankara, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0522-9432","authenticated-orcid":false,"given":"Dilek","family":"Pirim","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Institute of Health Sciences, Bursa Uludag University, 16059 Bursa, T\u00fcrkiye"},{"name":"Department of Molecular Biology and Genetics, Faculty of Arts & Science, Bursa Uludag University, 16059 Bursa, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2961-3970","authenticated-orcid":false,"given":"Sevinc","family":"Akcay","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Science and Art, K\u0131r\u015fehir Ahi Evran University, 40100 Kirsehir, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0599-5628","authenticated-orcid":false,"given":"Tugba Gurkok","family":"Tan","sequence":"additional","affiliation":[{"name":"Food and Agriculture Vocational School, Cankiri Karatekin University, 18702 Cankiri, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7982-5261","authenticated-orcid":false,"given":"Seda","family":"Ekici","sequence":"additional","affiliation":[{"name":"Veterinary Control Central Research Institute, 06220 Ankara, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6864-7711","authenticated-orcid":false,"given":"Sami","family":"Akbulut","sequence":"additional","affiliation":[{"name":"Department of Surgery and Liver Transplantation, Faculty of Medicine, Inonu University,   44280 Malatya, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.coph.2019.02.012","article-title":"Role of the P2X7 receptor in tumor-associated inflammation","volume":"47","author":"Adinolfi","year":"2019","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_2","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Yang, J., Tan, L., Shi, R., Hu, Q., Gu, Y., and Du, C. (2025). Vitamin D\/Vitamin D receptor signaling suppresses gastric cancer metastasis through autophagy-related protein 13\/Beclin1-mediated autophagy. Eurasian J. Med. Oncol., 025150096.","DOI":"10.36922\/EJMO025150096"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/s41575-025-01042-2","article-title":"Helicobacter pylori, microbiota and gastric cancer-principles of microorganism-driven carcinogenesis","volume":"22","author":"Wizenty","year":"2025","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1909459","DOI":"10.1080\/19490976.2021.1909459","article-title":"The interplay between Helicobacter pylori and gastrointestinal microbiota","volume":"13","author":"Chen","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1136\/gutjnl-2019-319696","article-title":"Effect of Helicobacter pylori on gastrointestinal microbiota: A population-based study in Linqu, a high-risk area of gastric cancer","volume":"69","author":"Guo","year":"2020","journal-title":"Gut"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Nasr, R., Shamseddine, A., Mukherji, D., Nassar, F., and Temraz, S. (2020). The Crosstalk between Microbiome and Immune Response in Gastric Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186586"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mohamed, A.S., Bhuju, R., Martinez, E., Basta, M., Deyab, A., Mansour, C., Tejada, D., Deshpande, V., Elias, S., and Nagesh, V.K. (2025). The Gut Microbiome\u2019s Impact on the Pathogenesis and Treatment of Gastric Cancer-An Updated Literature Review. Cancers, 17.","DOI":"10.3390\/cancers17172795"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wen, J., Lau, H.C., Peppelenbosch, M., and Yu, J. (2021). Gastric Microbiota beyond H. pylori: An Emerging Critical Character in Gastric Carcinogenesis. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111680"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1017\/erm.2021.8","article-title":"Integrating microbiome, transcriptome and metabolome data to investigate gastric disease pathogenesis: A concise review","volume":"23","author":"Doohan","year":"2021","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103956","DOI":"10.1016\/j.isci.2022.103956","article-title":"Multi-omics reveals microbiome, host gene expression, and immune landscape in gastric carcinogenesis","volume":"25","author":"Park","year":"2022","journal-title":"iScience"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20220528","DOI":"10.1515\/biol-2022-0528","article-title":"Integrated analysis of the microbiome and transcriptome in stomach adenocarcinoma","volume":"18","author":"Zhou","year":"2023","journal-title":"Open Life Sci."},{"key":"ref_13","first-page":"249","article-title":"1Alpha,25-dihydroxyvitamin D3 induces de novo E-cadherin expression in triple-negative breast cancer cells by CDH1-promoter demethylation","volume":"32","author":"Lopes","year":"2012","journal-title":"Anticancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Janssens, Y., Nielandt, J., Bronselaer, A., Debunne, N., Verbeke, F., Wynendaele, E., Van Immerseel, F., Vandewynckel, Y.P., De Tr\u00e9, G., and De Spiegeleer, B. (2018). Disbiome database: Linking the microbiome to disease. BMC Microbiol., 18.","DOI":"10.1186\/s12866-018-1197-5"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1136\/gutjnl-2017-314281","article-title":"Mucosal microbiome dysbiosis in gastric carcinogenesis","volume":"67","author":"Coker","year":"2018","journal-title":"Gut"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Dong, Z., Chen, B., Pan, H., Wang, D., Liu, M., Yang, Y., Zou, M., Yang, J., Xiao, K., and Zhao, R. (2019). Detection of Microbial 16S rRNA Gene in the Serum of Patients with Gastric Cancer. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00608"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1136\/gutjnl-2017-314205","article-title":"Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota","volume":"67","author":"Ferreira","year":"2018","journal-title":"Gut"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hu, Y.L., Pang, W., Huang, Y., Zhang, Y., and Zhang, C.J. (2018). The Gastric Microbiome Is Perturbed in Advanced Gastric Adenocarcinoma Identified Through Shotgun Metagenomics. Front. Cell Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00433"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kageyama, S., Takeshita, T., Takeuchi, K., Asakawa, M., Matsumi, R., Furuta, M., Shibata, Y., Nagai, K., Ikebe, M., and Morita, M. (2019). Characteristics of the Salivary Microbiota in Patients With Various Digestive Tract Cancers. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.01780"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e16626","DOI":"10.1097\/MD.0000000000016626","article-title":"Gut microbiota shifts in patients with gastric cancer in perioperative period","volume":"98","author":"Liang","year":"2019","journal-title":"Medicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.ebiom.2018.12.034","article-title":"Alterations of gastric mucosal microbiota across different stomach microhabitats in a cohort of 276 patients with gastric cancer","volume":"40","author":"Liu","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1007\/s10620-018-5411-y","article-title":"Intestinal Microbiota Is Altered in Patients with Gastric Cancer from Shanxi Province, China","volume":"64","author":"Qi","year":"2019","journal-title":"Dig. Dis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"W180","DOI":"10.1093\/nar\/gkx295","article-title":"MicrobiomeAnalyst: A web-based tool for comprehensive statistical, visual and meta-analysis of microbiome data","volume":"45","author":"Dhariwal","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1038\/s41388-022-02377-9","article-title":"Meta-analysis of mucosal microbiota reveals universal microbial signatures and dysbiosis in gastric carcinogenesis","volume":"41","author":"Liu","year":"2022","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Raoul, P., Maccauro, V., Cintoni, M., Scarpellini, E., Ianiro, G., Gasbarrini, A., Mele, M.C., and Rinninella, E. (2024). Microbiota-Gastric Cancer Interactions and the Potential Influence of Nutritional Therapies. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031679"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Vadhwana, B., Tarazi, M., Boshier, P.R., and Hanna, G.B. (2023). Evaluation of the Oesophagogastric Cancer-Associated Microbiome: A Systematic Review and Quality Assessment. Cancers, 15.","DOI":"10.3390\/cancers15102668"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ding, X.Y., Habimana, J.D., and Li, Z.Y. (2025). The role of DPP6 dysregulation in neuropathology: From synaptic regulation to disease mechanisms. Front. Cell. Neurosci., 19.","DOI":"10.3389\/fncel.2025.1547495"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12964-020-00553-6","article-title":"Low DLG2 gene expression, a link between 11q-deleted and MYCN-amplified neuroblastoma, causes forced cell cycle progression, and predicts poor patient survival","volume":"18","author":"Keane","year":"2020","journal-title":"Cell Commun. Signal."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/s41388-018-0444-4","article-title":"Cross-species genomics identifies DLG2 as a tumor suppressor in osteosarcoma","volume":"38","author":"Shao","year":"2019","journal-title":"Oncogene"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"108171","DOI":"10.1016\/j.celrep.2020.108171","article-title":"11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma","volume":"32","author":"Siaw","year":"2020","journal-title":"Cell Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1080\/15384047.2019.1579960","article-title":"MicroRNA-23a depletion promotes apoptosis of ovarian cancer stem cell and inhibits cell migration by targeting DLG2","volume":"20","author":"Zhuang","year":"2019","journal-title":"Cancer Biol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1002\/jcb.24009","article-title":"The JMJD2A demethylase regulates apoptosis and proliferation in colon cancer cells","volume":"113","author":"Kim","year":"2012","journal-title":"J. Cell. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Yao, W., Wang, J., Zhu, L., Jia, X., Xu, L., Tian, X., Hu, S., Wu, S., and Wei, L. (2021). Epigenetic Regulator KDM4D Restricts Tumorigenesis via Modulating SYVN1\/HMGB1 Ubiquitination Axis in Esophageal Squamous Cell Carcinoma. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.761346"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1128\/MCB.01094-10","article-title":"The ubiquitin-specific protease USP34 regulates axin stability and Wnt\/\u03b2-catenin signaling","volume":"31","author":"Lui","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e18945","DOI":"10.1016\/j.heliyon.2023.e18945","article-title":"Helicobacter pylori and epithelial mesenchymal transition in human gastric cancers: An update of the literature","volume":"9","author":"Nasr","year":"2023","journal-title":"Heliyon"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/jcb.24389","article-title":"Role of the Helicobacter pylori-induced inflammatory response in the development of gastric cancer","volume":"114","author":"Lamb","year":"2013","journal-title":"J. Cell. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"15711","DOI":"10.1038\/s41598-020-72594-3","article-title":"Helicobacter pylori infection induces STAT3 phosphorylation on Ser727 and autophagy in human gastric epithelial cells and mouse stomach","volume":"10","author":"Piao","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wu, M., Tian, C., Zou, Z., Jin, M., and Liu, H. (2024). Gastrointestinal Microbiota in Gastric Cancer: Potential Mechanisms and Clinical Applications-A Literature Review. Cancers, 16.","DOI":"10.3390\/cancers16203547"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Clark, A., and Mach, N. (2016). Role of Vitamin D in the Hygiene Hypothesis: The Interplay between Vitamin D, Vitamin D Receptors, Gut Microbiota, and Immune Response. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00627"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1158\/0008-5472.CAN-12-4300","article-title":"KDM4\/JMJD2 histone demethylases: Epigenetic regulators in cancer cells","volume":"73","author":"Berry","year":"2013","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2369336","DOI":"10.1080\/19490976.2024.2369336","article-title":"Intratumoral microbiome is associated with gastric cancer prognosis and therapy efficacy","volume":"16","author":"Wang","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1136\/jmg-2022-108733","article-title":"Decision-making and regret in patients with germline CDH1 variants undergoing prophylactic total gastrectomy","volume":"60","author":"Gamble","year":"2023","journal-title":"J. Med. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/aro2.70007","article-title":"Noncoding RNAs in host\u2013microbiota interaction","volume":"3","author":"Zhao","year":"2025","journal-title":"Anim. Res. One Health"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/5\/799\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:35:19Z","timestamp":1776857719000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/5\/799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,22]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["medicina62050799"],"URL":"https:\/\/doi.org\/10.3390\/medicina62050799","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,22]]}}}