Unveiling the shared genes between systemic sclerosis and lung cancer

The risk of lung cancer is significantly increased in patients with systemic sclerosis (SSc), yet the specific genes underlying this association remain unexplored. Our study aims to identify genes shared by SSc and lung cancer. We identified differentially expressed genes (DEGs) from SSc and lung adenocarcinoma (LUAD) datasets (SSc: GSE95065, LUAD: GSE136043) in the GEO database. We found shared genes by intersecting top genes in protein-protein interaction networks by the STRING database. The area under the ROC curve (AUC) was calculated for each shared gene in validation datasets (SSc: GSE231692; LUAD: GSE43458), identifying PRKG2 as the core shared gene. We used the UALCAN platform to assess PRKG2 expression in LUAD patients at various stages and lymph node metastasis states, and compared disease-free survival (DFS) between low and high PRKG2 expression LUAD groups. PRKG2 was overexpressed in A549 cells to study its impact on lung cancer cell proliferation and invasion <i>in vitro</i>. We identified seven shared genes (SCN7A, AGTR1, WIF1, PRKG2, LTF, AQP4, COL10A1), with the AUC for PRKG2 exceeding 0.93 in both diseases (SSc AUC = 0.973; LUAD AUC = 0.939). The PRKG2 expression levels of LUAD patients with different clinical stages and lymph node metastasis states were consistently lower than those observed in normal individuals. The DFS of LUAD patients in the high PRKG2 expression group was higher than that in the low expression group (<i>p</i> = 0.028). <i>In vitro</i> experiments confirmed elevated PRKG2 expression inhibits the proliferation and invasion of lung cancer cells. PRKG2 is one of the genes shared by SSc and lung cancer, affecting the proliferation and invasion of lung cancer cells.