# Identification of prognostic genes associated with tolerogenic dendritic cells in gastric cancer based on transcriptomic data

**Authors:** Shenyu Luo, Guozhi Yang, Yuhua Yuan, Yong Zhang, Yihua Kang, Zhengrong Wen, Wei Liu, Ying Liu, Xiaosheng Tan, Xiaosheng Tan, Xiaosheng Tan, Xiaosheng Tan, Xiaosheng Tan

PMC · DOI: 10.1371/journal.pone.0343688 · 2026-03-05

## TL;DR

This study identifies five genes linked to tolerogenic dendritic cells in gastric cancer, offering new insights for treatment strategies.

## Contribution

The study introduces a novel risk model based on five prognostic genes related to tolerogenic dendritic cells in gastric cancer.

## Key findings

- Five prognostic genes (CXCL1, INHBA, ASCL2, RNASE1, GPX3) were identified and used to construct a risk model.
- GPX3 showed strong positive associations with immune cells like regulatory T cells, while ASCL2 had weak associations.
- Drug sensitivity analysis revealed differing IC50 values for compounds like BIBW2992 and GSK269962A between risk groups.

## Abstract

Tolerogenic dendritic cells have a pivotal function in treating autoimmune illnesses, atopic diseases, and neoplasms. The precise mechanism by which Tolerogenic dendritic cells function in gastric cancer remains incompletely understood. Therefore, this research explored potential genes with prognostic value related to Tolerogenic dendritic cells in gastric cancer, to identify novel therapeutic targets that could provide valuable insights for the clinical treatment of gastric cancer.

Five prognostic genes (CXCL1, INHBA, ASCL2, RNASE1, and GPX3) were finally obtained to construct the risk model. Immune infiltration analysis revealed that GPX3 exhibited significant positive associations with various immune cell populations, particularly regulatory T cells. While ASCL2 was weakly associated with almost all immune cells. These results suggested that there was a complex correlation between prognostic genes and immune cells. The analysis of drug sensitivity demonstrated higher IC50 values for compounds such as BIBW2992 in high-risk group relative to low-risk group. A reverse pattern was observed for GSK269962A and similar drugs, which showed significantly higher IC50 values in low-risk group than high-risk group.

The present study revealed five prognostic genes and constructed a predictive model, which provided a theoretical basis for the correlation linking Tolerogenic dendritic cells to gastric cancer, and established potential therapeutic strategies in managing gastric cancer. Single-cell analysis revealed that INHBA, ASCL2, and CD36 exhibited marked differential expression in dendritic cells.

## Linked entities

- **Genes:** CXCL1 (C-X-C motif chemokine ligand 1) [NCBI Gene 2919], INHBA (inhibin subunit beta A) [NCBI Gene 3624], ASCL2 (achaete-scute family bHLH transcription factor 2) [NCBI Gene 430], RNASE1 (ribonuclease A family member 1, pancreatic) [NCBI Gene 6035], GPX3 (glutathione peroxidase 3) [NCBI Gene 2878], CD36 (CD36 molecule (CD36 blood group)) [NCBI Gene 948]
- **Chemicals:** BIBW2992 (PubChem CID 10184653), GSK269962A (PubChem CID 16095342)
- **Diseases:** gastric cancer (MONDO:0001056)

## Full-text entities

- **Genes:** WNT5A (Wnt family member 5A) [NCBI Gene 7474] {aka hWNT5A}, ASCL2 (achaete-scute family bHLH transcription factor 2) [NCBI Gene 430] {aka ASH2, HASH2, MASH2, bHLHa45}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, RENBP (renin binding protein) [NCBI Gene 5973] {aka RBP, RNBP}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, KDM5B (lysine demethylase 5B) [NCBI Gene 10765] {aka CT31, JARID1B, MRT65, PLU-1, PLU1, PPP1R98}, ERBB4 (erb-b2 receptor tyrosine kinase 4) [NCBI Gene 2066] {aka ALS19, HER4, p180erbB4}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, SCIN (scinderin) [NCBI Gene 85477], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, INHBA (inhibin subunit beta A) [NCBI Gene 3624] {aka EDF, FRP}, PKP2 (plakophilin 2) [NCBI Gene 5318] {aka ARVD9}, 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}, CXCL1 (C-X-C motif chemokine ligand 1) [NCBI Gene 2919] {aka FSP, GRO1, GROa, MGSA, MGSA-a, NAP-3}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, SMYD3 (SET and MYND domain containing 3) [NCBI Gene 64754] {aka KMT3E, ZMYND1, ZNFN3A1, bA74P14.1}, RNASE1 (ribonuclease A family member 1, pancreatic) [NCBI Gene 6035] {aka RAC1, RIB1, RNS1}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, GATA3 (GATA binding protein 3) [NCBI Gene 2625] {aka HDR, HDRS}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, INHBE (inhibin subunit beta E) [NCBI Gene 83729], INHBB (inhibin subunit beta B) [NCBI Gene 3625], CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, FOXA2 (forkhead box A2) [NCBI Gene 3170] {aka HNF-3-beta, HNF3B, TCF3B}, CXCR2 (C-X-C motif chemokine receptor 2) [NCBI Gene 3579] {aka CD182, CDw128b, CMKAR2, IL8R2, IL8RA, IL8RB}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, GPX3 (glutathione peroxidase 3) [NCBI Gene 2878] {aka GPx-P, GSHPx-3, GSHPx-P}, RNASE2 (ribonuclease A family member 2) [NCBI Gene 6036] {aka EDN, RAF3, RNS2}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}
- **Diseases:** atopic diseases (MESH:D006969), HRG (MESH:D008228), hypertrophic cardiomyopathy (MESH:D002312), GC (MESH:D013274), autoimmune illnesses (MESH:D001327), arrhythmogenic right ventricular cardiomyopathy (MESH:D019571), obesity (MESH:D009765), BC (MESH:D001943), gastric (MESH:D013272), SLE (MESH:D008180), Adenocarcinomas of the Esophagus (MESH:C562730), liver cancer (MESH:D006528), metabolic disorders (MESH:D008659), colon cancer (MESH:D015179), tumorigenic (MESH:D002471), deaths (MESH:D003643), metastasis (MESH:D009362), DC (MESH:D054221), airway inflammation (MESH:D007249), head and neck cancer (MESH:D006258), Cancer (MESH:D009369), lung cancer (MESH:D008175), cardiovascular disease (MESH:D002318), infection (MESH:D007239), dilated cardiomyopathy (MESH:D002311)
- **Chemicals:** VX.680 (MESH:C484810), LPS (MESH:D008070), lipid (MESH:D008055), glutathione (MESH:D005978), steroid (MESH:D013256), BIBW2992 (MESH:D000077716), m6A (MESH:C005955), water (MESH:D014867), GW.441756 (MESH:C000606649), alcohol (MESH:D000438), H2O2 (MESH:D006861), DMOG (-), N6-methyladenosine (MESH:C010223), lipid hydroperoxides (MESH:D008054), Fatty acid (MESH:D005227), GSK269962A (MESH:C516969), dexamethasone (MESH:D003907), lactic acid (MESH:D019344), dasatinib (MESH:D000069439)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Helicobacter pylori (species) [taxon 210]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12962506/full.md

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Source: https://tomesphere.com/paper/PMC12962506