The identification of key driver genes in idiopathic pulmonary fibrosis (IPF) could help identify new therapeutic targets for the disease, according to a new study published in the journal BMC Pulmonary Medicine.
The researchers identified subgroups with different pathobiological characteristics and clinical prognostic scores while molecularly analyzing IPF lung tissues.
The identification of these discrete molecular subtypes of the disease could help in patient stratification and ensure they receive customized therapies. They can also ensure better clinical trial design.
IPF is a difficult disease with a high clinical burden and unmet treatment needs. It is known that some fibrotic diseases consist of distinct molecular subgroups. Researchers from Korea led by Ki-Jo Kim MD, PhD, identified differentially expressed genes in the lung tissue of 585 patients with IPF and 362 healthy controls.
Read more about IPF prognosis
They identified 2967 upregulated genes in IPF with the core molecular network of the disease featuring the p53 signaling pathway and cellular senescence. The researchers then grouped the patients into 2 groups, with those in the first group being more enriched in the p53 signaling pathway, and those in the second group more enriched for cellular senescence.
Patients in the first group had a worse prognostic score. The researchers also found that the p53 signaling pathway correlated with a decline in forced vital capacity, a key measure of lung function, and the carbon monoxide diffusion capacity of the lungs as well as the activation of cellular senescence.
“[Key driver genes] and target molecules were identified in the defined disease module,” the researchers wrote. They reported that inhibiting cyclin-dependent kinases and histone deacetylases showed great promise in controlling fibrosis.
“This not only explained the limitations of current pharmacotherapies but also provided insights into navigating new drug therapies,” they said.
Kim SK, Jung SM, Park KS, Kim KJ. Integrative analysis of lung molecular signatures reveals key drivers of idiopathic pulmonary fibrosis. BMC Pulm Med. 2021;21:404. doi:10.1186/s12890-021-01749-3