Cartilage oligomeric matrix protein in pulmonary arterial hypertension associated with lung adenocarcinoma

Pulmonary arterial hypertension (PAH) associated with lung adenocarcinoma (LUAD) is a pathological condition that arises during LUAD progression. Cartilage oligomeric matrix protein (COMP) is an important extracellular matrix (ECM) glycoprotein and may mediate the relationship between PAH and LUAD.

We collected chest-enhanced CT scans from clinical LUAD patients and screened for PAH using the Pulmonary Artery(PA)/ Aortic(A) ratio. By analyzing the TCGA-LUAD, GSE140797, and VSMCPRG gene sets, we identified gene signatures associated with PAH in LUAD. Additionally, we analyzed pathological samples, serum samples, EdU cell proliferation assays, and measurements of pulmonary artery vascular contractile function.

Our study retrospectively collected relevant data from 421 patients in our department between 2020 and 2025. In the LUAD group, the PA/A ratio ≥ 1 was significantly higher than in both the adenocarcinoma in situ (AIS) group and the Benign nodules group. Immunohistochemical(IHC) analysis of 17 pathological samples revealed significant upregulation of COMP in the LUAD group compared with normal lung tissue. Serum COMP optical density (OD) values were significantly higher in LUAD groups than in control groups, in both humans and mice.EdU assays demonstrated that human pulmonary artery smooth muscle cells (HPASMCs) co-cultured with COMP showed significantly higher proliferation rates than the control group. To assess the effect of COMP on pulmonary artery vasculature, rat and human experiments showed that the contractile force in the COMP group was significantly greater than that in the control group.

These findings suggest that LUAD may be associated with PAH, and that COMP may promote PAH development by enhancing pulmonary artery smooth muscle cell proliferation and vascular contractility.