# Advances in Spatial Multi-Omics in Gastric Cancer **Authors:** Hongfei Yan, Yang Liu PMC · DOI: 10.3390/cells15060535 · 2026-03-17 ## TL;DR This review discusses how spatial multi-omics can better understand gastric cancer by capturing molecular and spatial details of tumors and their environment. ## Contribution The paper reviews advances in spatial multi-omics technologies and their potential to improve gastric cancer classification and treatment strategies. ## Key findings - Spatial multi-omics can reveal tumor heterogeneity and microenvironment interactions missed by traditional methods. - These technologies help identify new biomarkers and mechanisms of therapy resistance in gastric cancer. - Current challenges include technical limitations and the need for clinical translation of spatial profiling. ## Abstract 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. ## Linked entities - **Diseases:** gastric cancer (MONDO:0001056) ## Full-text entities - **Genes:** GLI2 (GLI family zinc finger 2) [NCBI Gene 2736] {aka CJS, HPE9, PHS2, THP1, THP2}, NDUFAB1 (NADH:ubiquinone oxidoreductase subunit AB1) [NCBI Gene 4706] {aka ACP, ACP1, FASN2A, SDAP}, FGFR2 (fibroblast growth factor receptor 2) [NCBI Gene 2263] {aka BBDS, BEK, BFR-1, CD332, CEK3, CFD1}, MZB1 (marginal zone B and B1 cell specific protein) [NCBI Gene 51237] {aka MEDA-7, PACAP, pERp1}, NAMPT (nicotinamide phosphoribosyltransferase) [NCBI Gene 10135] {aka 1110035O14Rik, PBEF, PBEF1, VF, VISFATIN}, ERBB3 (erb-b2 receptor tyrosine kinase 3) [NCBI Gene 2065] {aka ErbB-3, FERLK, HER3, LCCS2, MDA-BF-1, VSCN1}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, WNT3A (Wnt family member 3A) [NCBI Gene 89780], LGALS3 (galectin 3) [NCBI Gene 3958] {aka CBP35, GAL3, GALBP, GALIG, L31, LGALS2}, TPT1 (tumor protein, translationally-controlled 1) [NCBI Gene 7178] {aka HRF, TCTP, p02, p23}, PSG2 (pregnancy specific beta-1-glycoprotein 2) [NCBI Gene 5670] {aka CEA, PSBG2, PSG1}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}, CXCR5 (C-X-C motif chemokine receptor 5) [NCBI Gene 643] {aka BLR1, CD185, MDR15}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, FABP4 (fatty acid binding protein 4) [NCBI Gene 2167] {aka A-FABP, AFABP, ALBP, HEL-S-104, aP2}, EGR1 (early growth response 1) [NCBI Gene 1958] {aka AT225, G0S30, KROX-24, NGFI-A, TIS8, ZIF-268}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, HLA-E (major histocompatibility complex, class I, E) [NCBI Gene 3133] {aka HLA-6.2, QA1}, ACTA2 (actin alpha 2, smooth muscle) [NCBI Gene 59] {aka ACTSA, SMDYS}, MMP7 (matrix metallopeptidase 7) [NCBI Gene 4316] {aka MMP-7, MPSL1, PUMP-1}, CCR2 (C-C motif chemokine receptor 2) [NCBI Gene 729230] {aka CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2}, MDM2 (MDM2 proto-oncogene) [NCBI Gene 4193] {aka ACTFS, HDMX, LSKB, hdm2}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, AREG (amphiregulin) [NCBI Gene 374] {aka AR, AREGB, CRDGF, SDGF}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, FCER1G (Fc epsilon receptor Ig) [NCBI Gene 2207] {aka FCRG}, KLRC1 (killer cell lectin like receptor C1) [NCBI Gene 3821] {aka CD159A, NKG2, NKG2A}, PDGFD (platelet derived growth factor D) [NCBI Gene 80310] {aka IEGF, MSTP036, SCDGF-B, SCDGFB}, THBS1 (thrombospondin 1) [NCBI Gene 7057] {aka THBS, THBS-1, TSP, TSP-1, TSP1}, SFRP2 (secreted frizzled related protein 2) [NCBI Gene 6423] {aka FRP-2, SARP1, SDF-5}, CSF1 (colony stimulating factor 1) [NCBI Gene 1435] {aka CSF-1, MCSF, PG-M-CSF}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, WNT6 (Wnt family member 6) [NCBI Gene 7475], CD160 (CD160 molecule) [NCBI Gene 11126] {aka BY55, NK1, NK28}, GLI1 (GLI family zinc finger 1) [NCBI Gene 2735] {aka GLI, PAPA8, PPD1}, GDF15 (growth differentiation factor 15) [NCBI Gene 9518] {aka GDF-15, HG, MIC-1, MIC1, NAG-1, PDF}, RRM2 (ribonucleotide reductase regulatory subunit M2) [NCBI Gene 6241] {aka C2orf48, R2, RR2, RR2M}, ITGB5 (integrin subunit beta 5) [NCBI Gene 3693], TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, ZFP36 (ZFP36 zinc finger CCCH-type) [NCBI Gene 7538] {aka G0S24, GOS24, NUP475, RNF162A, TIS11, TTP}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, RHOA (ras homolog family member A) [NCBI Gene 387] {aka ARH12, ARHA, EDFAOB, RHO12, RHOH12}, ITGAV (integrin subunit alpha V) [NCBI Gene 3685] {aka CD51, IDNDC, MSK8, VNRA, VTNR}, GPRC5A (G protein-coupled receptor class C group 5 member A) [NCBI Gene 9052] {aka GPCR5A, PEIG-1, RAI3, RAIG1, TIG1}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, LAMP3 (lysosome associated membrane protein 3) [NCBI Gene 27074] {aka CD208, DC LAMP, DC-LAMP, DCLAMP, LAMP, LAMP-3}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, ARG1 (arginase 1) [NCBI Gene 383], CXCL13 (C-X-C motif chemokine ligand 13) [NCBI Gene 10563] {aka ANGIE, ANGIE2, BCA-1, BCA1, BLC, BLR1L}, ALKBH1 (alkB homolog 1, histone H2A dioxygenase) [NCBI Gene 8846] {aka ABH, ABH1, ALKBH, alkB, hABH}, RSPO3 (R-spondin 3) [NCBI Gene 84870] {aka CRISTIN1, PWTSR, THSD2}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, ACKR1 (atypical chemokine receptor 1 (Duffy blood group)) [NCBI Gene 2532] {aka CCBP1, CD234, DARC, DARC/ACKR1, Dfy, FY}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, CCR10 (C-C motif chemokine receptor 10) [NCBI Gene 2826] {aka GPR2}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19} - **Diseases:** hypoxia (MESH:D000860), Tumors (MESH:D009369), precancerous (MESH:D011230), EBV (MESH:D020031), Inflammatory (MESH:D007249), LNmet (MESH:D008207), brain metastases (MESH:D001932), necrotic (MESH:D009336), H. pylori infection (MESH:D016481), Alzheimer's disease (MESH:D000544), liver metastases (MESH:D009362), Peritoneal (MESH:D010538), MSI (MESH:C564543), gastric oncogenesis (MESH:D063646), digestive malignancy (MESH:D004828), GSRC (MESH:D018279), adenocarcinoma (MESH:D000230), serrated lesions (MESH:D009059), TLSs (MESH:D000072717), injury to (MESH:D014947), Microsatellite Instability (MESH:D053842), benign gastrointestinal diseases (MESH:D005767), TLS-deficient (MESH:D007153), CIN (MESH:D043171), N (MESH:C536108), cytotoxicity (MESH:D064420), Diffuse Gastric Cancer (MESH:D013274), GS (MESH:D060050), tumorigenic (MESH:D002471), PCC (MESH:D000270) - **Chemicals:** Cabozantinib (MESH:C558660), pertuzumab (MESH:C485206), peptides (MESH:D010455), amino acid (MESH:D000596), Vardenafil (MESH:D000069058), AFB1 (MESH:D016604), arachidonic acid (MESH:D016718), SHR-1701 (MESH:C000723862), Vitamin B6 (MESH:D025101), Glycerophospholipid (MESH:D020404), proline (MESH:D011392), glucose (MESH:D005947), Pembrolizumab (MESH:C582435), nucleotide (MESH:D009711), PE (MESH:C483858), poly(T) (MESH:D011071), Avelumab (MESH:C000609138), metal (MESH:D008670), carbohydrate (MESH:D002241), uracil (MESH:D014498), histidine (MESH:D006639), Trastuzumab (MESH:D000068878), rapamycin (MESH:D020123), Regorafenib (MESH:C559147), glutamine (MESH:D005973), polyamines (MESH:D011073), Lapatinib (MESH:D000077341), PE-NMe (-), TCA (MESH:D014238), cholesterol sulfate (MESH:C007045), lipid (MESH:D008055), glycans (MESH:D011134), platinum (MESH:D010984), SM (MESH:D013109), osalmid (MESH:C005414) - **Species:** Helicobacter pylori (species) [taxon 210], Homo sapiens (human, species) [taxon 9606] - **Mutations:** H1047X, E542K ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13025482/full.md --- Source: https://tomesphere.com/paper/PMC13025482