Researchers uncovered a genetic connection between systemic sclerosis and lung adenocarcinoma. The study identified protein kinase cGMP-dependent type II (PRKG2) as a pivotal gene linking these diseases, paving the way for novel diagnostic and therapeutic approaches.

Using bioinformatics tools, the team analyzed datasets from the GEO database (SSc: GSE95065, LUAD: GSE136043) and validated their findings with independent datasets (SSc: GSE231692, LUAD: GSE43458). Seven shared genes were identified, with PRKG2 emerging as the most significant marker, demonstrating diagnostic accuracy with area under the ROC curve (AUC) scores of 0.97 for systemic sclerosis (SSc) and 0.94 for lung adenocarcinoma (LUAD).

PRKG2 expression was significantly lower in LUAD patients compared to healthy controls. While higher PRKG2 expression correlated with improved disease-free survival (DFS), no significant association with overall survival (OS) was observed, underscoring its potential as a diagnostic rather than a prognostic marker.

Published in Frontiers in Medicine, the study also highlights PRKG2’s role in ferroptosis, a form of iron-dependent cell death linked to fibrosis in SSc and tumor suppression in LUAD. The gene’s modulation of immune cells, such as macrophages and dendritic cells, further underscores its therapeutic relevance.

Laboratory experiments confirmed that overexpressed PRKG2 suppresses LUAD cell proliferation, invasion, and migration. SSc patients face an increased risk of lung cancer due to prolonged disease duration, smoking, and immune system dysregulation, which suggests the need for targeted approaches.

These findings provide new insights into the shared genetic mechanisms of SSc and LUAD. PRKG2 has the potential to serve as a target for future research and interventions aimed at improving outcomes in patients affected by these challenging conditions.

The authors disclosed no conflicts of interest in the study.