Potential of C-X-C motif chemokine ligand 1/8/10/12 as diagnostic and prognostic biomarkers in idiopathic pulmonary arterial hypertension

Abstract

Objective: This study aimed to evaluate the clinical role of C-X-C motif chemokine ligand (CXCL) family members in idiopathic pulmonary arterial hypertension (IPAH) patients. Methods: CXCL1, CXCL8, CXCL10 and CXCL12 expressions in the serum samples of IPAH patients (N = 39) and age-/gender-matched controls (N = 40) were detected by enzyme-linked immunosorbent assay. In IPAH patients, clinical features were collected, and survival information was documented. Results: CXCL1 (P < 0.001), CXCL8 (P = 0.001), CXCL10 (P < 0.001) and CXCL12 (P < 0.001) were increased in IPAH patients compared with controls, and receiver's operating characteristic curves showed that their combination was highly correlated with IPAH risk (area under curve: 0.881, 95% confidence interval: 0.805–0.958). Meanwhile, CXCL1 was positively correlated with mean pulmonary artery pressure (mPAP) (P = 0.029) and high-sensitive C-reactive protein (HsCRP) (P = 0.015); CXCL8 was positively correlated with mPAP (P = 0.044) and HsCRP (P = 0.018) but negatively correlated with 6-minute walk test (6MWT) distance (P = 0.029); CXCL10 was positively correlated with mean right artery pressure (P = 0.002); and CXCL12 was positively correlated with World Health Organization functional class (P = 0.047), mPAP (P = 0.009), pulmonary vascular resistance (P = 0.004) and HsCRP (P = 0.003) but negatively correlated with 6MWT distance (P = 0.003) in IPAH patients. Moreover, CXCL12 was negatively correlated with overall survival (OS) (P = 0.025), whereas CXCL1, CXCL8 and CXCL10 only showed minor tendencies to be negatively correlated with OS in IPAH patients without statistical significance (all P > 0.05). Conclusion: CXCL1, CXCL8, CXCL10 and CXCL12 associate with increased IPAH risk, unfavourable clinical features; besides, CXCL12 correlates with worse OS in IPAH patients.