# Comprehensive analysis of molecular characteristic and clinical prognosis of CD8+ T cell related genes in idiopathic pulmonary fibrosis

**Authors:** Lin Feng, Jiabo Yuan, Xiaobing Dou, Yanlin Liu, Simone Agostini, Simone Agostini, Simone Agostini, Simone Agostini

PMC · DOI: 10.1371/journal.pone.0328250 · PLOS One · 2025-07-31

## TL;DR

This study explores how CD8+ T cell-related genes affect the progression and prognosis of idiopathic pulmonary fibrosis, identifying potential biomarkers for predicting outcomes.

## Contribution

The study identifies CXCR4, GPR56, and PAK1 as independent prognostic factors linked to CD8+ T cells in IPF.

## Key findings

- CD8+ T cell-related genes were associated with IPF prognosis and used to establish molecular typing characteristics.
- CXCR4, GPR56, and PAK1 were validated as independent prognostic factors in IPF.
- Abnormal expression of these genes was confirmed in TGF-β1 treated IPF models at both mRNA and protein levels.

## Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening interstitial lung disease whose pathogenesis remains unclear. There is evidence showing the possible role of CD8+ T cells in the pathogenesis of IPF and the correlation with the clinical symptoms of IPF. In order to further explore the role of CD8+ T cells in IPF, we screened CD8+ T cell related genes (CRG) that are associated with IPF prognosis, and established the molecular typing characteristics of IPF. Subsequently, CXCR4, GPR56 and PAK1 were screened as independent prognostic factors. Expression profiles and multivariate analysis coefficients were used to establish and validate prognostic features of IPF. Immuno-infiltration characteristics of the established feature were also analyzed. Subsequent in vitro experiments verified the abnormal expressions of three independent prognostic factors in TGF-β1 treated IPF model at protein and mRNA levels. Our findings shed new light on the important role of CD8+ T cells in the pathogenesis of IPF and provide potential targets for predicting prognosis and possible future clinical applications.

## Linked entities

- **Genes:** CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852], ADGRG1 (adhesion G protein-coupled receptor G1) [NCBI Gene 9289], PAK1 (p21 (RAC1) activated kinase 1) [NCBI Gene 5058]
- **Diseases:** idiopathic pulmonary fibrosis (MONDO:0800029)

## Full-text entities

- **Genes:** CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, ADGRG1 (adhesion G protein-coupled receptor G1) [NCBI Gene 9289] {aka BFPP, BPPR, CDCBM14B, CDCBM15A, GPR56, TM7LN4}, CAT (catalase) [NCBI Gene 847], MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, CDC42 (cell division cycle 42) [NCBI Gene 998] {aka CDC42Hs, G25K, TKS}, CD14 (CD14 molecule) [NCBI Gene 929], CHD7 (chromodomain helicase DNA binding protein 7) [NCBI Gene 55636] {aka CRG, HH5, IS3, KAL5}, CD163 (CD163 molecule) [NCBI Gene 9332] {aka M130, MM130, SCARI1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, RAC1 (Rac family small GTPase 1) [NCBI Gene 5879] {aka MIG5, MRD48, Rac-1, TC-25, p21-Rac1}, PAK1 (p21 (RAC1) activated kinase 1) [NCBI Gene 5058] {aka IDDMSSD, PAKalpha, alpha-PAK, p65-PAK}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}
- **Diseases:** tumor (MESH:D009369), dyspnea (MESH:D004417), immune dysregulation (OMIM:614878), fibrosis (MESH:D005355), autoimmune diseases (MESH:D001327), sepsis (MESH:D018805), ORCID iD (MESH:C535742), respiratory failure (MESH:D012131), IPF (MESH:D054990), Idiopathic pulmonary fibrosisPLOS (MESH:D065627), pulmonary fibrosis (MESH:D011658), interstitial lung disease (MESH:D017563), fibrotic disease (MESH:D004194)
- **Chemicals:** penicillin (MESH:D010406), streptomycin (MESH:D013307), CO2 (MESH:D002245), PONE-D-25-16281 (-), -D (MESH:D003903), carbon (MESH:D002244), PVDF (MESH:C024865), beta-alanine (MESH:D015091), GTP (MESH:D006160), SDS (MESH:D012967), Sirolimus (MESH:D020123), pirfenidone (MESH:C093844), TRIzol (MESH:C411644)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** MRC-5 — Homo sapiens (Human), Finite cell line (CVCL_0440)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12312977/full.md

## References

55 references — full list in the complete paper: https://tomesphere.com/paper/PMC12312977/full.md

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Source: https://tomesphere.com/paper/PMC12312977