# Revealing the significance of tissue-resident memory T cells in lung adenocarcinoma through bioinformatic analysis and experimental validation

**Authors:** Zhuoqi Li, Mei Tian, Yuanhui Yang, Yuanyuan Wang, Lu Zhang, Fujing Huang, Xiao Wen, Xiaoshu Yin, Xiaoyan Lin, Yuan Tian

PMC · DOI: 10.3389/fimmu.2025.1600863 · 2025-06-26

## TL;DR

This study identifies a set of genes in lung tissue-resident memory T cells that can predict survival and treatment outcomes for lung adenocarcinoma patients.

## Contribution

A novel prognostic signature based on lung TRM cell-specific genes for predicting LUAD outcomes and treatment response.

## Key findings

- 130 differentially expressed lung TRM cell-specific genes were identified, with 14 forming a prognostic signature.
- The signature accurately predicted survival and immunotherapy response in LUAD patients, with AUCs up to 0.867 in validation.
- TYMS was identified as a key gene linked to LUAD progression and cell proliferation.

## Abstract

To investigate the functions of lung TRM cells in the development and treatment of lung adenocarcinoma (LUAD).

R-language bioinformatics analysis was applied to obtain differentially expressed (DE) lung TRM cell-specific genes and a related prognostic signature, which were further validated using external datasets, immunohistochemical staining images, and biological experiments.

A total of 130 DE lung TRM cell-specific genes were identified, 14 of which were involved in the prognostic signature, including SLC16A3, ARHGAP11A, PTTG1, DTL, GPRIN1, EXO1, GAPDH, TYMS, DAPK2, CCL20, HLA-DQA1, ADAM12, ALOX5AP and OASL. The signature was efficient and robust in predicting the overall survival and anti-PD-1/PD-L1 immunotherapeutic outcomes of patients with LUAD. The AUCs for predicting the 1-, 3-, and 5-year survival rates were 0.688, 0.698, and 0.648, respectively, in the training cohort, and were 0.867, 0.662, and 0.672, respectively, in the validation cohort. The signature also had predictive value for the sensitivity of patients to chemical drugs. TYMS was a hub gene in the prognostic signature, and was strongly associated with LUAD progression and cell proliferation in the experimental validation.

The lung TRM cell-related prognostic signature is an effective tool for predicting the prognosis and therapeutic outcomes of patients with LUAD.

## Linked entities

- **Genes:** SLC16A3 (solute carrier family 16 member 3) [NCBI Gene 9123], ARHGAP11A (Rho GTPase activating protein 11A) [NCBI Gene 9824], PTTG1 (PTTG1 regulator of sister chromatid separation, securin) [NCBI Gene 9232], DTL (denticleless E3 ubiquitin protein ligase adapter) [NCBI Gene 51514], GPRIN1 (G protein regulated inducer of neurite outgrowth 1) [NCBI Gene 114787], EXO1 (exonuclease 1) [NCBI Gene 9156], GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597], TYMS (thymidylate synthetase) [NCBI Gene 7298], DAPK2 (death associated protein kinase 2) [NCBI Gene 23604], CCL20 (C-C motif chemokine ligand 20) [NCBI Gene 6364], HLA-DQA1 (major histocompatibility complex, class II, DQ alpha 1) [NCBI Gene 3117], ADAM12 (ADAM metallopeptidase domain 12) [NCBI Gene 8038], ALOX5AP (arachidonate 5-lipoxygenase activating protein) [NCBI Gene 241], OASL (2'-5'-oligoadenylate synthetase like) [NCBI Gene 8638]
- **Diseases:** lung adenocarcinoma (MONDO:0005061)

## Full-text entities

- **Genes:** DTL (denticleless E3 ubiquitin protein ligase adapter) [NCBI Gene 51514] {aka CDT2, DCAF2, L2DTL, RAMP}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, ARHGAP11A (Rho GTPase activating protein 11A) [NCBI Gene 9824] {aka GAP (1-12)}, TYMS (thymidylate synthetase) [NCBI Gene 7298] {aka DKCD, HST422, TMS, TS}, SLC16A3 (solute carrier family 16 member 3) [NCBI Gene 9123] {aka MCT 3, MCT 4, MCT-3, MCT-4, MCT3, MCT4}, ADAM12 (ADAM metallopeptidase domain 12) [NCBI Gene 8038] {aka ADAM12-OT1, CAR10, MCMP, MCMPMltna, MLTN, MLTNA}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, ALOX5AP (arachidonate 5-lipoxygenase activating protein) [NCBI Gene 241] {aka FLAP}, HLA-DQA1 (major histocompatibility complex, class II, DQ alpha 1) [NCBI Gene 3117] {aka CELIAC1, DQ-A1, DQA1, HLA-DQA, HLA-DQA1*}, PTTG1 (PTTG1 regulator of sister chromatid separation, securin) [NCBI Gene 9232] {aka EAP1, ECRAR, HPTTG, PTTG, TUTR1}, DAPK2 (death associated protein kinase 2) [NCBI Gene 23604] {aka DRP-1, DRP1}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, OASL (2'-5'-oligoadenylate synthetase like) [NCBI Gene 8638] {aka OASL1, OASLd, TRIP-14, TRIP14, p59 OASL, p59-OASL}, CCL20 (C-C motif chemokine ligand 20) [NCBI Gene 6364] {aka CKb4, Exodus, LARC, MIP-3-alpha, MIP-3a, MIP3A}, GPRIN1 (G protein regulated inducer of neurite outgrowth 1) [NCBI Gene 114787] {aka GRIN1}, EXO1 (exonuclease 1) [NCBI Gene 9156] {aka HEX1, hExoI}
- **Diseases:** LUAD (MESH:D000077192)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

12 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12240778/full.md

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Source: https://tomesphere.com/paper/PMC12240778