NLRC3: A Novel Noninvasive Biomarker for Pulmonary Hypertension Diagnosis
Li-huang Zha1,3, Jun Zhou2, Tang-zhiming Li1, Hui Luo1, Jing-ni He1, Lin Zhao1, Zai-xin Yu1,*
1Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China 2Medical Science Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China 3Department of Cardiology, Zhuzhou Central Hospital, Zhuzhou, Hunan, China
The nucleotide-oligomerization domain (NOD)-like receptor subfamily C3 (NLRC3) is a newly discovered and incompletely characterized member of the NLR family which negatively regulates inflammatory responses. Inflammation is considered a critical pathogenesis in pulmonary hypertension (PH). This is the first study to hypothesize that NLRC3 is closely correlated with PH. Total of 43 PH patients who were diagnosed by right heart catheterization (RHC) and 20 age-matched healthy control subjects were included. Echocardiographic variables and blood biochemical parameters were tested. Results of World Health Organization functional class (WHOFC), Borg dyspnea score and 6-minute walk tests (6MWT) were recorded. Mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) were measured from RHC. Serum NLRC3 concentrations were detected by ELISA. ROC curve analysis was used to evaluate the diagnostic value of NLRC3 concentrations in PH. We found that serum NLRC3 concentration was significantly decreased in PH compared to the healthy control group. Serum NLRC3 concentration correlated negatively with mPAP and PVR. In addition, a negative correlation between serum NLRC3 concentration and WHOFC were detected. We proposed a cut-off value of 2.897ng/mL for serum NLRC3 concentration which was able to predict PH with 88% sensitivity and 85% specificity. In conclusion, NLRC3 concentrations in PH were significantly decreased, suggesting that NLRC3 may potentially be a diagnosis index and represent a prognostic factor for PH patients.
Table 1 Baseline characteristics of the study population.
Figure 1. Serum NLRC3 concentrations were reduced in PH patients versus controls
The scatter plots on the left and the Box-and-Whisker plots above on the right provided data for serum NLRC3 concentrations (Fig. 1A and 1B) in control subjects (n = 20), and patients with PH (n = 43). Serum NLRC3 concentrations decreased in PH severity. The scatter plots on the left and the Boxand-Whisker plots on the right below provided data for serum NLRC3 concentrations (Fig. 1C and 1D) according to WHO FC. Control: n=20; WHOFC II: n = 6; WHOFCIII-IV: n = 37. The scatter plots showed the mean±SD; the Box-and-Whisker plots showed the median with IQR±5-95th percentile. *p<0.05, ***p<0.0001.
Figure 2. Serum NLRC3 concentrations negatively correlated with mPAP, PVR and WHOFC
Serum NLRC3 concentrations significantly negatively correlated with mPAP (r = -0.517, p=0.0004, Fig. 2A), PVR (r = -0.308, p=0.045, Fig. 2B) and WHOFC (rho=-0.729, p=0.007, Fig. 2C) in PH patients.
Table 2 Correlations between NLRC3 and hemodynamic parameters obtained by RHC in PH patients.
Table 3 Correlations between NLRC3 and echocardiography parameters.
Figure 3. The cut-off value of Serum NLRC3 concentration was 2.90ng/mL to distinguish PH patients from healthy people
The area under the curve was 0.9175 (95%CI 0.8487 to 0.9827), 2.897 ng/mL is the maximum cut-off value, at this point the sensitivity of PH was 88%, and the specificity was 85%
Table 4 Correlations between NLRC3 and functional indexes in PH patients.
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