Exploring PDLIM2 as a prognostic biomarker and therapeutic target in lung adenocarcinoma
8 affiliations
- 1Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA USA
- 2UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA USA
- 3Caris Life Sciences, Phoenix, AZ USA
- 4Georgetown University, Washington, DC USA
- 5Penn State Cancer Institute, Penn State College of Medicine, Hershey, PA USA
- 6Montefiore Medical Center, Bronx, New York, NY USA
- 7Department of Immunology and Immune Therapeutics, Keck School of Medicine, University of Southern California, Los Angeles, CA USA
- 8Hastings Center for Pulmonary Research, Keck School of Medicine, University of Southern California, Los Angeles, CA USA
Abstract
Background: While PDZ-LIM domain-containing protein (PDLIM2) suppresses lung cancer, its clinical significance and therapeutic potential remain to be fully explored.
Methods: Next-generation sequencing and immunohistochemistry of programmed death ligand 1 (PD-L1) were performed on lung adenocarcinoma (LUAD) tissues from 15,765 patients. PDLIM2 gene therapy was tested in syngeneic LUAD mouse models using intravenous nano-complexed plasmid DNA, alone or with chemoimmunotherapy.
Results: PDLIM2-high tumors were more common in primary/local biopsies versus metastatic samples (73.1% vs 53.0%; p < 0.001). High PDLIM2 expression was linked to lower mutation rates in RB1, TP53, SMARCA4, STK11, and KEAP1, but increased EGFR mutations (all p < 0.01). PDLIM2-high tumors also showed increased immune cell infiltration, T cell-inflamed scores, and PD-L1 positivity (all p < 0.008). High PDLIM2 was associated with improved survival (24.1 vs 18.1 months; p < 0.001, HR = 0.84) and remained prognostic in multivariate analysis (HR = 0.88, 95% CI 0.83–0.93), as well as with longer pembrolizumab time, especially with platinum-based therapy (p = 0.012, HR = 0.867). In two LUAD mouse models, nanoPDLIM2 improved median overall survival versus chemoimmunotherapy alone (10–12.5 vs 8–9 days; N = 8; p = 0.0001, 0.0003).
Conclusion: PDLIM2 is a promising prognostic biomarker in LUAD linked to immune-receptive tumors. Preclinically, PDLIM2-based therapy enhances chemoimmunotherapy efficacy, though its predictive role warrants further evaluation.
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BibTeX
@article{ashouri2026exploring,
title = {{Exploring PDLIM2 as a prognostic biomarker and therapeutic target in lung adenocarcinoma}},
author = {Karam Ashouri and Fan Sun and Harris Krause and Andrew Elliott and Stephen V. Liu and Patrick C. Ma and Balazs Halmos and Gutian Xiao and Ari Vanderwalde and Jorge J. Nieva and Zhaoxia Qu},
journal = {British Journal of Cancer},
year = {2026},
month = aug,
doi = {10.1038/s41416-026-03570-3},
url = {https://doi.org/10.1038/s41416-026-03570-3},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Exploring PDLIM2 as a prognostic biomarker and therapeutic target in lung adenocarcinoma
AU - Karam Ashouri
AU - Fan Sun
AU - Harris Krause
AU - Andrew Elliott
AU - Stephen V. Liu
AU - Patrick C. Ma
AU - Balazs Halmos
AU - Gutian Xiao
AU - Ari Vanderwalde
AU - Jorge J. Nieva
AU - Zhaoxia Qu
PY - 2026
DA - 2026/08/08
JO - British Journal of Cancer
DO - 10.1038/s41416-026-03570-3
UR - https://doi.org/10.1038/s41416-026-03570-3
AB - Background: While PDZ-LIM domain-containing protein (PDLIM2) suppresses lung cancer, its clinical significance and therapeutic potential remain to be fully explored. Methods: Next-generation sequencing and immunohistochemistry of programmed death ligand 1 (PD-L1) were performed on lung adenocarcinoma (LUAD) tissues from 15,765 patients. PDLIM2 gene therapy was tested in syngeneic LUAD mouse models using intravenous nano-complexed plasmid DNA, alone or with chemoimmunotherapy. Results: PDLIM2-high tumors were more common in primary/local biopsies versus metastatic samples (73.1% vs 53.0%; p < 0.001). High PDLIM2 expression was linked to lower mutation rates in RB1, TP53, SMARCA4, STK11, and KEAP1, but increased EGFR mutations (all p < 0.01). PDLIM2-high tumors also showed increased immune cell infiltration, T cell-inflamed scores, and PD-L1 positivity (all p < 0.008). High PDLIM2 was associated with improved survival (24.1 vs 18.1 months; p < 0.001, HR = 0.84) and remained prognostic in multivariate analysis (HR = 0.88, 95% CI 0.83–0.93), as well as with longer pembrolizumab time, especially with platinum-based therapy (p = 0.012, HR = 0.867). In two LUAD mouse models, nanoPDLIM2 improved median overall survival versus chemoimmunotherapy alone (10–12.5 vs 8–9 days; N = 8; p = 0.0001, 0.0003). Conclusion: PDLIM2 is a promising prognostic biomarker in LUAD linked to immune-receptive tumors. Preclinically, PDLIM2-based therapy enhances chemoimmunotherapy efficacy, though its predictive role warrants further evaluation.
SN - 0007-0920
SN - 1532-1827
ER -