NDLI: PTK2-associated gene signature could predict the prognosis of IPF

Content Provider	Springer Nature : BioMed Central
Author	Feng, Anlin Caro, Yesenia Moreno Gardner, Colin Grischo, Garrett Liang, Ying Wickremasinghe, Praveen D. Polmann, Michaela Kala, Mrinalini Marlowe, Timothy Black, Stephen M. Knox, Kenneth S. Wang, Ting
Abstract	Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with a poor prognosis. Current/available clinical prediction tools have limited sensitivity and accuracy when evaluating clinical outcomes of IPF. Research has shown that focal adhesion kinase (FAK), produced by the protein tyrosine kinase 2 (PTK2) gene, is crucial in IPF development. FAK activation is a characteristic of lesional fibroblasts; Thus, FAK may be a valuable therapeutic target or prognostic biomarker for IPF. This study aimed to create a gene signature based on PTK2-associated genes and microarray data from blood cells to predict disease prognosis in patients with IPF. PTK2 levels were found to be higher in lung tissues of IPF patients compared to healthy controls, and PTK2 inhibitor Defactinib was found to reduce TGFβ-induced FAK activation and increase α-smooth muscle actin. Although the blood PTK2 levels were higher in IPF patients, blood PTK level alone could not predict IPF prognosis. From 196 PTK2-associated genes, 11 genes were prioritized to create a gene signature (PTK2 molecular signature) and a risk score system using univariate and multivariate Cox regression analysis. Patients were divided into high-risk and low-risk groups using PTK2 molecular signature. Patients in the high-risk group experienced decreased survival rates compared to patients in the low-risk group across all discovery and validation cohorts. Further functional enrichment and immune cell proportion analyses revealed that the PTK2 molecular signature strongly reflected the activation levels of immune pathways and immune cells. These findings suggested that PTK2 is a molecular target of IPF and the PTK2 molecular signature is an effective IPF prognostic biomarker.
Related Links	https://respiratory-research.biomedcentral.com/counter/pdf/10.1186/s12931-023-02582-4.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12931-023-02582-4
Journal	Respiratory Research
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2023-12-06
Access Restriction	Open
Subject Keyword	Pneumology Respiratory System Pneumology/Respiratory System
Content Type	Text
Resource Type	Article
Subject	Pulmonary and Respiratory Medicine
Journal Impact Factor	4.7/2023
5-Year Journal Impact Factor	5.3/2023

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