{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:50:08Z","timestamp":1789145408183,"version":"build-2803163510"},"reference-count":143,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Maximizing Investigators Research Award","award":["R35 GM150838"],"award-info":[{"award-number":["R35 GM150838"]}]},{"name":"Maximizing Investigators Research Award","award":["NIH R01 HL173271"],"award-info":[{"award-number":["NIH R01 HL173271"]}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"crossref","award":["#IRG-21-132-60-IRG"],"award-info":[{"award-number":["#IRG-21-132-60-IRG"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Gastric cancer (GC) remains a major global health burden, with its unfavorable prognosis primarily driven by extensive tumor heterogeneity. Traditional bulk omics, while informative, are inherently limited by the averaging effect of diverse cell populations and fail to capture the critical spatial molecular disparities within the tumor and its microenvironment (TME). Single-cell omics can capture cellular heterogeneity but lack spatial context. Therefore, there is an urgent clinical need for spatial multi-omics to provide a high-definition dissection of GC heterogeneity and to optimize therapeutic efficacy. This review first outlines briefly the evolution of spatial technologies, including transcriptomics, proteomics, metabolomics, genomics and epigenomics, and their transformative applications in GC research. We further explore how these platforms refine molecular classification beyond traditional models, identify next-generation biomarkers, and decode the intricate cellular interactions governing immune evasion and metastasis. Next, we highlight the pivotal role of spatial profiling in unravelling the multidimensional mechanisms of resistance to chemotherapy, targeted therapy and immunotherapy. Finally, we address current technical bottlenecks and discuss prospects for clinical translation.<\/jats:p>","DOI":"10.3390\/cells15060535","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T12:42:16Z","timestamp":1773751336000},"page":"535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Advances in Spatial Multi-Omics in Gastric Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Hongfei","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1830-948X","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA"},{"name":"Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA"},{"name":"Yale Cancer Center, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. 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