Blood CDC42 overexpression is associated with an increased risk of acute exacerbation, inflammation and disease severity in patients with chronic obstructive pulmonary disease

Abstract

It has been previously reported that cell division control 42 (CDC42) protein can regulate macrophage recruitment, T cell-associated inflammation and lung injury. However, its role in chronic obstructive pulmonary disease (COPD) remain poorly understood. Therefore, the present study aimed to investigate the possible association among CDC42 expression, the risk of acute exacerbation and disease features in patients with COPD. Peripheral blood mononuclear cells (PBMCs) and serum samples were collected from 60 patients with acute exacerbation COPD (AE-COPD), 60 patients with stable COPD (S-COPD) and 60 healthy control (HCs) individuals. The mRNA expression levels of CDC42 in PBMCs were then measured using reverse transcription-quantitative PCR. The serum levels of TNF-α, IL-1β, IL-6 and IL-17 were measured using ELISA. The results showed that the expression of CDC42 was dysregulated among patients with AE-COPD and S-COPD compared with that in HCs. Specifically, the expression level of CDC42 was the highest in patients with AE-COPD, followed by those with S-COPD and the lowest in HCs (P<0.001). Furthermore, receiver operating characteristic curve analysis demonstrated that CDC42 expression was associated with an increased risk of acute exacerbation in COPD with an area under curve of 0.690 (95% confidence interval=0.595-0.785). CDC42 was found to be positively associated with Global Initiative for Chronic Obstructive Lung Disease staging in patients with AE-COPD (P<0.01) and S-COPD (P<0.05). Additionally, CDC42 expression associated positively with the serum levels of TNF-α, IL-1β, IL-6 and IL-17 in patients with AE-COPD (all P<0.05). However, this association was weaker in patients with S-COPD and became negligible in HCs. In conclusion, data from the present study suggest that CDC42 is associated with an increased risk of acute exacerbation, inflammation and disease severity in patients with COPD, implicating its application as a potential biomarker for COPD.

Keywords: acute exacerbation risk; cell division cycle 2; chronic obstructive pulmonary disease; disease severity; inflammation.

Figure 1

Comparison of CDC42 expression among HCs, patients with AD-COPD and S-COPD. CDC42, cell division cycle 42; COPD, chronic obstructive pulmonary disease; S-COPD, stable COPD; AE-COPD, acute exacerbation COPD; HCs, health controls. ^*P<0.05 AE-COPD vs. HCs; ^#P<0.05, AE-COPD vs. S-COPD; ^$P <0.05, S-COPD vs. HCs.

Figure 2

Receiver operating characteristic curve for the ability of differentiating patients with AE-COPD from patients with S-COPD using CDC42 expression. CDC42, cell division cycle 42; COPD, chronic obstructive pulmonary disease; AE-COPD, acute exacerbation COPD; S-COPD, stable COPD; AUC, area under curve; CI, confidence interval.

Figure 3

Association between CDC42 expression and GOLD staging. Association of CDC42 expression with GOLD staging in (A) patients with AE-COPD and (B) patients with S-COPD. CDC42, cell division cycle 42; COPD, chronic obstructive pulmonary disease; AE-COPD, acute exacerbation COPD; S-COPD, stable COPD; GOLD, Global Initiative for Chronic Obstructive Lung Disease. ^*P<0.05 Stage III vs. Stage I, ^#P<0.05 Stage II vs. Stage I.

Figure 4

Correlation between CDC42 expression and each of the inflammatory cytokines. Correlation analysis of CDC42 expression with (A) TNF-α, (B) IL-1β, (C) IL-6 and (D) IL-17 in patients with acute exacerbation chronic obstructive pulmonary disease. CDC42: cell division cycle 42.