# Integrated transcriptomics and molecular docking identify hub genes and statin regulators in Helicobacter pylori-associated gastric mucosal pathogenesis **Authors:** Minglin Zhang, Xue He, Xuelin Zhao, Ting Cai, Xiaoming Liu, Fen Wang PMC · DOI: 10.3389/fcimb.2026.1688009 · Frontiers in Cellular and Infection Microbiology · 2026-02-13 ## TL;DR This study combines gene expression and drug interaction data to identify key genes and statin regulators involved in H. pylori-related stomach diseases. ## Contribution The study integrates transcriptomics and molecular docking to reveal hub genes and potential statin regulators in H. pylori pathogenesis. ## Key findings - 107 co-expressed differentially expressed genes were identified in H. pylori-infected gastric cells. - 20 hub genes were prioritized, enriched in NF-κB, TNF, and IL-17 signaling pathways. - Statin drugs like simvastatin and atorvastatin were predicted to interact with key hub genes. ## Abstract Helicobacter pylori (H. pylori), a spiral Gram-negative bacterium colonizing gastric mucosa, damages epithelial cells, driving chronic gastritis, peptic ulcers, and gastric cancer. Mechanisms of its malignant transformation remain unclear. We identified differentially expressed genes (DEGs) and hub genes, pathway enrichment analysis, transcription factors (TFs), small-molecule drug and molecular docking prediction using gastric epithelial cells (GECs) infected with H. pylori strain 26695 and clinical sample datasets. H. pylori infection of GECs, multiple signaling pathways were activated, including the p53, MAPK, TNF, IL-17, PI3K-Akt and NF-κB signaling, DNA replication, Apoptosis, Cell cycle, Necroptosis. A total of 107 co-expressed DEGs were identified in vitro and in vivo. Using Cytoscape, 20 hub genes were prioritized: TNF, CXCL8, NFKBIA, IRF1, ICAM1, TNFAIP3, BIRC3, CXCL1, ITGAM, RELB, CXCL2, CCL20, NFKB2, EGR1, CDKN1A, IRAK2, JAK1, NFKBIE, TRAF1, and JUNB. These hub genes were enriched in NF-κB, TNF and IL-17 signaling, and responses to bacterial pathogens or lipopolysaccharide. Further analysis identified 9 upregulated TFs: VDR, SPI1, ETS2, STAT1, E2F1, PML, ETS1, BRCA1, MYC, and 4 downregulated TFs: ING4, CEBPD, HSF1, JUN. To explore potential therapeutic interventions, we performed small-molecule drug prediction and molecular docking for hub genes revealed: Simvastatin: Linked to CCL20, NFKBIA, and ICAM1. Atorvastatin: Associated with CDKN1A, ICAM1, and TNF. TPCA-1: Targeting JAK1. These findings provide a theoretical foundation for further investigation into the molecular mechanisms underlying H. pylori-related diseases. ## Linked entities - **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124], CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576], NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792], IRF1 (interferon regulatory factor 1) [NCBI Gene 3659], ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383], TNFAIP3 (TNF alpha induced protein 3) [NCBI Gene 7128], BIRC3 (baculoviral IAP repeat containing 3) [NCBI Gene 330], CXCL1 (C-X-C motif chemokine ligand 1) [NCBI Gene 2919], ITGAM (integrin subunit alpha M) [NCBI Gene 3684], RELB (RELB proto-oncogene, NF-kB subunit) [NCBI Gene 5971], CXCL2 (C-X-C motif chemokine ligand 2) [NCBI Gene 2920], CCL20 (C-C motif chemokine ligand 20) [NCBI Gene 6364], NFKB2 (nuclear factor kappa B subunit 2) [NCBI Gene 4791], EGR1 (early growth response 1) [NCBI Gene 1958], CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026], IRAK2 (interleukin 1 receptor associated kinase 2) [NCBI Gene 3656], JAK1 (Janus kinase 1) [NCBI Gene 3716], NFKBIE (NFKB inhibitor epsilon) [NCBI Gene 4794], TRAF1 (TNF receptor associated factor 1) [NCBI Gene 7185], JUNB (JunB proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3726], VDR (vitamin D receptor) [NCBI Gene 7421], SPI1 (Spi-1 proto-oncogene) [NCBI Gene 6688], ETS2 (ETS proto-oncogene 2, transcription factor) [NCBI Gene 2114], STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772], E2F1 (E2F transcription factor 1) [NCBI Gene 1869], PML (PML nuclear body scaffold) [NCBI Gene 5371], ETS1 (ETS proto-oncogene 1, transcription factor) [NCBI Gene 2113], BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672], MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609], ING4 (inhibitor of growth family member 4) [NCBI Gene 51147], CEBPD (CCAAT enhancer binding protein delta) [NCBI Gene 1052], HSF1 (heat shock transcription factor 1) [NCBI Gene 3297], JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725] - **Chemicals:** Simvastatin (PubChem CID 54454), Atorvastatin (PubChem CID 60823), TPCA-1 (PubChem CID 9903786) - **Diseases:** chronic gastritis (MONDO:0005001), gastric cancer (MONDO:0001056) - **Species:** Helicobacter pylori (taxon 210) ## Full-text entities - **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, SNAI1 (snail family transcriptional repressor 1) [NCBI Gene 6615] {aka SLUGH2, SNA, SNAH, SNAIL, SNAIL1, dJ710H13.1}, ETS2 (ETS proto-oncogene 2, transcription factor) [NCBI Gene 2114] {aka ETS2IT1}, ITGAM (integrin subunit alpha M) [NCBI Gene 3684] {aka CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, PTPRH (protein tyrosine phosphatase receptor type H) [NCBI Gene 5794] {aka R-PTP-H, SAP1}, JUNB (JunB proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3726] {aka AP-1}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, FBXO31 (F-box protein 31) [NCBI Gene 79791] {aka FBX14, FBXO14, Fbx31, MRT45, pp2386}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, ITGB2 (integrin subunit beta 2) [NCBI Gene 3689] {aka CD18, LAD, LCAMB, LFA-1, MAC-1, MF17}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792] {aka EDAID2, IKBA, MAD-3, NFKBI}, ING4 (inhibitor of growth family member 4) [NCBI Gene 51147] {aka my036, p29ING4}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, CXCL2 (C-X-C motif chemokine ligand 2) [NCBI Gene 2920] {aka CINC-2a, GRO2, GROb, MGSA-b, MIP-2a, MIP2}, CFB (complement factor B) [NCBI Gene 629] {aka AHUS4, ARMD14, BF, BFD, CFAB, CFBD}, NAPA (NSF attachment protein alpha) [NCBI Gene 8775] {aka SNAPA}, IL32 (interleukin 32) [NCBI Gene 9235] {aka IL-32alpha, IL-32beta, IL-32delta, IL-32gamma, NK4, TAIF}, TRIB1 (tribbles pseudokinase 1) [NCBI Gene 10221] {aka C8FW, GIG-2, GIG2, SKIP1, TRB-1, TRB1}, RELB (RELB proto-oncogene, NF-kB subunit) [NCBI Gene 5971] {aka I-REL, IMD53, IREL, REL-B}, DRAM1 (DNA damage regulated autophagy modulator 1) [NCBI Gene 55332] {aka DRAM}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, GDF15 (growth differentiation factor 15) [NCBI Gene 9518] {aka GDF-15, HG, MIC-1, MIC1, NAG-1, PDF}, ANGPTL4 (angiopoietin like 4) [NCBI Gene 51129] {aka ARP4, FIAF, HARP, HFARP, NL2, PGAR}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, MMP10 (matrix metallopeptidase 10) [NCBI Gene 4319] {aka SL-2, STMY2}, NFKBIE (NFKB inhibitor epsilon) [NCBI Gene 4794] {aka IKBE}, FSTL1 (follistatin like 1) [NCBI Gene 11167] {aka FRP, FSL1, OCC-1, OCC1, tsc36}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, CagA [NCBI Gene 48200769], DMBT1 (deleted in malignant brain tumors 1) [NCBI Gene 1755] {aka GP340, SAG, SALSA, muclin}, SAT1 (spermidine/spermine N1-acetyltransferase 1) [NCBI Gene 6303] {aka DC21, KFSD, KFSDX, SAT, SSAT, SSAT-1}, LRP8 (LDL receptor related protein 8) [NCBI Gene 7804] {aka APOER2, HSZ75190, LRP-8, MCI1}, SPI1 (Spi-1 proto-oncogene) [NCBI Gene 6688] {aka AGM10, OF, PU.1, SFPI1, SPI-1, SPI-A}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, NFKB2 (nuclear factor kappa B subunit 2) [NCBI Gene 4791] {aka CVID10, H2TF1, LYT-10, LYT10, NF-kB2, p100}, PML (PML nuclear body scaffold) [NCBI Gene 5371] {aka MYL, PP8675, RNF71, TRIM19}, INHBE (inhibin subunit beta E) [NCBI Gene 83729], CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, RUNX3 (RUNX family transcription factor 3) [NCBI Gene 864] {aka AML2, CBFA3, PEBP2aC}, E2F1 (E2F transcription factor 1) [NCBI Gene 1869] {aka E2F-1, RBAP1, RBBP3, RBP3}, UPP1 (uridine phosphorylase 1) [NCBI Gene 7378] {aka UDRPASE, UP, UPASE, UPP}, REG4 (regenerating family member 4) [NCBI Gene 83998] {aka GISP, REG-IV, RELP}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, MMP7 (matrix metallopeptidase 7) [NCBI Gene 4316] {aka MMP-7, MPSL1, PUMP-1}, HKDC1 (hexokinase domain containing 1) [NCBI Gene 80201] {aka RP92}, JAK1 (Janus kinase 1) [NCBI Gene 3716] {aka AIIDE, JAK1A, JAK1B, JTK3}, ATF3 (activating transcription factor 3) [NCBI Gene 467], TRAF1 (TNF receptor associated factor 1) [NCBI Gene 7185] {aka EBI6, MGC:10353}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, NONO (non-POU domain containing octamer binding) [NCBI Gene 4841] {aka MRXS34, NMT55, NRB54, P54, P54NRB, PPP1R114} - **Diseases:** T-cell leukemia virus 1 infection (MESH:D015458), IBD (MESH:D015212), bacterial (MESH:D001424), gastric mucosal damage (MESH:D013272), chronic gastritis (MESH:D005756), ICH (MESH:D002543), precancerous lesions (MESH:D011230), programmed cell death (MESH:D003643), metastasis (MESH:D009362), Legionellosis (MESH:D007876), Rheumatoid arthritis (MESH:D001172), XL (MESH:D000080345), peptic ulcers (MESH:D010437), infected (MESH:D007239), carcinogenesis (MESH:D063646), hypoxic (MESH:D002534), GC (MESH:D013274), pancreatic cancer (MESH:D010190), H. pylori (MESH:D016481), Epstein-Barr virus infection (MESH:D020031), gastric inflammation (MESH:D007249), atrophic gastritis (MESH:D005757), PCD (MESH:D007619), atrophy (MESH:D001284), cancer (MESH:D009369) - **Chemicals:** UNC-0321 (MESH:C551961), LPS (MESH:D008070), CO2 (MESH:D002245), threonine (MESH:D013912), Simvastatin (MESH:D019821), bismuth (MESH:D001729), Atorvastatin (MESH:D000069059), prunetin (MESH:C083295), tivozanib (MESH:C553176), BRD-K64835161 (-), Serine (MESH:D012694), omeprazole (MESH:D009853), urea (MESH:D014508), gefitinib (MESH:D000077156), capecitabine (MESH:D000069287), aspartate (MESH:D001224), Terpenoid (MESH:D013729), calpeptin (MESH:C071482), TPCA-1 (MESH:C499326), NVP-AUY922 (MESH:C528044), LY-364947 (MESH:C506615), Glycine (MESH:D005998), cholesterol (MESH:D002784), geldanamycin (MESH:C001277), amoxicillin (MESH:D000658), glutamate (MESH:D018698), cosmosiin (MESH:C057792), paraffin (MESH:D010232), clarithromycin (MESH:D017291), Alanine (MESH:D000409) - **Species:** Helicobacter pylori 26695 (strain) [taxon 85962], Homo sapiens (human, species) [taxon 9606], Helicobacter pylori (species) [taxon 210], Mus musculus (house mouse, species) [taxon 10090] - **Cell lines:** HGC27 — Homo sapiens (Human), Gastric carcinoma, Cancer cell line (CVCL_1279), GES-1 — Homo sapiens (Human), Transformed cell line (CVCL_EQ22), AGS — Homo sapiens (Human), Gastric adenocarcinoma, Cancer cell line (CVCL_0139), TPCA-1 — Mus musculus (Mouse), Hybridoma (CVCL_C7RB), MKN45 — Homo sapiens (Human), Gastric adenocarcinoma, Cancer cell line (CVCL_0434) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12945777/full.md ## Figures 10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12945777/full.md ## References 80 references — full list in the complete paper: https://tomesphere.com/paper/PMC12945777/full.md --- Source: https://tomesphere.com/paper/PMC12945777