# Identification and Verification of Anoikis‐related Genes in Epilepsy Through Bioinformatics Analysis

**Authors:** Haoxuan Zeng, Yanling Yuan, Tian Tan, Wenbing Zhou, Xianju Zhou, Xinhao Chen

PMC · DOI: 10.1002/brb3.71273 · Brain and Behavior · 2026-02-16

## TL;DR

This study identifies five genes linked to anoikis in epilepsy, offering new insights into its molecular causes and potential treatments.

## Contribution

The novel contribution is the identification of five anoikis-related genes as potential biomarkers and therapeutic targets for epilepsy.

## Key findings

- Five key anoikis-related genes (ANKRD13C, PIK3R1, BSG, CEACAM6, BRMS1) were identified as potential biomarkers for epilepsy.
- A risk score model based on these genes showed high diagnostic efficiency.
- MPEP, LY-341495, and MDL-28170 were suggested as potential therapeutic agents.

## Abstract

Epilepsy is a significant neurological disorder characterized by a complex etiology. Understanding the molecular mechanisms, notably those implicated in the immune system and anoikis, is crucial for developing targeted therapies against epilepsy.

First, two epilepsy‐related transcriptomic datasets (GSE143272 and GSE4290) were selected from the GEO database; then, the differentially expressed genes (DEGs) were identified. Focusing on anoikis in epilepsy, we screened out anoikis‐related genes (ARGs). Bioinformatics analysis and machine learning were employed for comprehensive analysis, and the research results were validated in an epileptic mouse model.

A total of 3525 DEGs from the GSE143272 and GSE4290 datasets were identified, and a total of 24 ARGs were obtained. The five key differentially expressed ARGs (DE‐ARGs) were screened through machine learning analysis, including ANKRD13C, PIK3R1, BSG, CEACAM6, and BRMS1; these DE‐ARGs emerged as potential biomarkers for epilepsy and were involved in various signaling pathways and immune cell activities, and results were further experimentally validated. Besides, the risk score model based on the DE‐ARGs demonstrated high diagnostic efficiency; moreover, connectivity map database analysis suggested MPEP, LY‐341495, and MDL‐28170 as potential therapeutic agents.

This study identified the five ARGs as potential therapeutic targets, highlighting the role of anoikis in epilepsy pathogenesis. Our result provides a novel insight into the molecular landscape of epilepsy and paves the way for further exploration and the development of more effective treatment strategies.

A total of 3525 differentially expressed genes (DEGs) from two epilepsy‐related transcriptomic datasets (GSE143272 and GSE4290) were screened, and a further 24 anoikis‐related genes (ARGs) were obtained. The five key differentially expressed ARGs (DE‐ARGs), including ANKRD13C, PIK3R1, BSG, CEACAM6, and BRMS1, were identified through machine learning (LASSO regression and WGCNA analysis).

## Linked entities

- **Genes:** ANKRD13C (ankyrin repeat domain 13C) [NCBI Gene 81573], PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295], BSG (basigin (Ok blood group)) [NCBI Gene 682], CEACAM6 (CEA cell adhesion molecule 6) [NCBI Gene 4680], BRMS1 (BRMS1 transcriptional repressor and anoikis regulator) [NCBI Gene 25855]
- **Chemicals:** MPEP (PubChem CID 3025961), LY-341495 (PubChem CID 9819927), MDL-28170 (PubChem CID 72430)
- **Diseases:** epilepsy (MONDO:0005027)

## Full-text entities

- **Genes:** Brms1 (breast cancer metastasis-suppressor 1) [NCBI Gene 107392], STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772] {aka CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, ANKRD13C (ankyrin repeat domain 13C) [NCBI Gene 81573] {aka dJ677H15.3}, CHEK2 (checkpoint kinase 2) [NCBI Gene 11200] {aka CDS1, CHK2, HuCds1, LFS2, PP1425, RAD53}, MBP (myelin basic protein) [NCBI Gene 4155], KCNB1 (potassium voltage-gated channel subfamily B member 1) [NCBI Gene 3745] {aka DEE26, DRK1, Kv2.1}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, ANXA5 (annexin A5) [NCBI Gene 308] {aka ANX5, CPB-I, ENX2, HEL-S-7, PP4, RPRGL3}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, PAK1 (p21 (RAC1) activated kinase 1) [NCBI Gene 5058] {aka IDDMSSD, PAKalpha, alpha-PAK, p65-PAK}, STAT5A (signal transducer and activator of transcription 5A) [NCBI Gene 6776] {aka MGF, STAT5}, BRMS1 (BRMS1 transcriptional repressor and anoikis regulator) [NCBI Gene 25855], HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, CST7 (cystatin F) [NCBI Gene 8530] {aka CMAP}, Grm2 (glutamate metabotropic receptor 2) [NCBI Gene 24415] {aka mGlu2}, EEF2K (eukaryotic elongation factor 2 kinase) [NCBI Gene 29904] {aka CaMKIII, HSU93850, eEF-2K}, ITGA5 (integrin subunit alpha 5) [NCBI Gene 3678] {aka CD49e, FNRA, VLA-5, VLA5A}, Bsg (basigin) [NCBI Gene 12215] {aka CD147, EMMPRIN, HT-7}, FLT1 (fms related receptor tyrosine kinase 1) [NCBI Gene 2321] {aka FLT, FLT-1, VEGFR-1, VEGFR1}, PLCG2 (phospholipase C gamma 2) [NCBI Gene 5336] {aka APLAID, FCAS3, PLC-IV, PLC-gamma-2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, TNR (tenascin R) [NCBI Gene 7143] {aka NEDSTO, TN-R}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, Ankrd13c (ankyrin repeat domain 13c) [NCBI Gene 433667], PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, STAT4 (signal transducer and activator of transcription 4) [NCBI Gene 6775] {aka DPMC, SLEB11}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, TGFBR1 (transforming growth factor beta receptor 1) [NCBI Gene 7046] {aka AAT5, ACVRLK4, ALK-5, ALK5, ESS1, LDS1}, BMF (Bcl2 modifying factor) [NCBI Gene 90427], SERPINA2 (serpin family A member 2 (gene/pseudogene)) [NCBI Gene 390502] {aka ARGS, ATR, PIL, SERPINA2P, psiATR}, ADGRV1 (adhesion G protein-coupled receptor V1) [NCBI Gene 84059] {aka FEB4, GPR98, MASS1, USH2B, USH2C, VLGR1}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, Cd4 (Cd4 molecule) [NCBI Gene 24932] {aka W3/25, p55}, Grm3 (glutamate metabotropic receptor 3) [NCBI Gene 24416] {aka mGluR3}, ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}, NRGN (neurogranin) [NCBI Gene 4900] {aka RC3, hng}, VN1R17P (vomeronasal 1 receptor 17 pseudogene) [NCBI Gene 441931] {aka GPCR}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, PIK3CD (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta) [NCBI Gene 5293] {aka APDS, IMD14, IMD14A, IMD14B, P110DELTA, PI3K}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, PRL (prolactin) [NCBI Gene 5617] {aka GHA1, pPRL}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CLEC4D (C-type lectin domain family 4 member D) [NCBI Gene 338339] {aka CD368, CLEC-6, CLEC6, CLECSF8, Dectin-3, MCL}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, CSF1R (colony stimulating factor 1 receptor) [NCBI Gene 1436] {aka BANDDOS, C-FMS, CD115, CSF-1R, CSFR, FIM2}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, SLC1A2 (solute carrier family 1 member 2) [NCBI Gene 6506] {aka DEE41, EAAT2, EIEE41, GLT-1, GLT1, HBGT}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, DLGAP1 (DLG associated protein 1) [NCBI Gene 9229] {aka DAP-1, DAP-1-ALPHA, DAP-1-BETA, DAP1, DLGAP1A, DLGAP1B}, PDK4 (pyruvate dehydrogenase kinase 4) [NCBI Gene 5166], ABL2 (ABL proto-oncogene 2, non-receptor tyrosine kinase) [NCBI Gene 27] {aka ABLL, ARG}, CD247 (CD247 molecule) [NCBI Gene 919] {aka CD3-ZETA, CD3H, CD3Q, CD3Z, CD3ZETA, IMD25}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, CEACAM6 (CEA cell adhesion molecule 6) [NCBI Gene 4680] {aka CD66c, CEAL, NCA, NCA-50/90}
- **Diseases:** hypoxia (MESH:D000860), epilepticus (MESH:D013226), convulsive seizures (MESH:D012640), neurological disorder (MESH:D009461), neuroinflammation (MESH:D000090862), temporal lobe epilepsy (MESH:D004833), cancer (MESH:D009369), diabetes (MESH:D003920), melanoma (MESH:D008545), inflammation (MESH:D007249), neurodegeneration (MESH:D019636), tissue damage (MESH:D017695), absence epilepsy (MESH:D004832), mesial temporal lobe epilepsy (MESH:C566903), breast cancer (MESH:D001943), neuronal damage (MESH:D009410), acidosis (MESH:D000138), cardiovascular diseases (MESH:D002318), brain injury (MESH:D001930), brain disease (MESH:D001927), Epilepsy (MESH:D004827), hippocampal sclerosis (MESH:D000092223)
- **Chemicals:** galactose (MESH:D005690), diazepam (MESH:D003975), water (MESH:D014867), LY-341495 (MESH:C114624), pentose phosphate (MESH:D010428), Methyl scopolamine (MESH:D019832), pyruvate (MESH:D019289), calcium (MESH:D002118), ROS (MESH:D017382), PVDF (MESH:C024865), MDL-28170 (MESH:C058076), heme (MESH:D006418), pilocarpine (MESH:D010862), MPEP (MESH:C121465), Ca 2 + (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Helicobacter pylori (species) [taxon 210], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** WAG/Rij — Wallago attu (Helicopter catfish), Spontaneously immortalized cell line (CVCL_1H01)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12910123/full.md

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12910123/full.md

## References

60 references — full list in the complete paper: https://tomesphere.com/paper/PMC12910123/full.md

---
Source: https://tomesphere.com/paper/PMC12910123