Sensitive Biomarker Analysis of Xue-Fu-Zhu-Yu Capsule for Patients with Qi Stagnation and Blood Stasis Pattern: A Nested Case-Control Study

Guang Chen; Haoqiang He; Kun Hu; Jialiang Gao; Jun Li; Mei Han; Jie Wang

doi:10.1155/2019/7182865

Sensitive Biomarker Analysis of Xue-Fu-Zhu-Yu Capsule for Patients with Qi Stagnation and Blood Stasis Pattern: A Nested Case-Control Study

Evid Based Complement Alternat Med. 2019 Nov 18:2019:7182865. doi: 10.1155/2019/7182865. eCollection 2019.

Authors

Guang Chen^{1

2}, Haoqiang He^{1

2}, Kun Hu¹, Jialiang Gao¹, Jun Li¹, Mei Han³, Jie Wang¹

Affiliations

¹ Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
² Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.
³ Center for Evidence-based Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.

Abstract

Objectives: To identify the sensitive biomarker to predict the effectiveness of Xue-Fu-Zhu-Yu capsules (XFZYC).

Methods: This nested case-control study included 5 patients with response to XFZYC in the treatment group, 5 patients with no response to XFZYC also in the treatment group, and 5 patients in the control group treated with placebo who participated in the previous RCT. The mRNAs, miRNAs, lncRNAs, and circRNAs were sequenced by next-generation sequencing and differential-expressed (DE) RNAs were identified if p value ≤ 0.05 and fold change ≥2, bioinformatics analysis was conducted in terms of function annotations and signaling pathways, and then sensitive biomarker was analyzed based on real-time PCR.

Results: The distributions of clinical characteristics between the selected participants from treatment group and placebo group were well balanced. A total of 1156 DE RNAs, 388 miRNAs, 1954 lncRNAs, and 560 circRNAs were identified, which was associated the mechanism of XFZYC and composed the targeted potential biomarkers for further real-time PCR. The DE RNAs were enriched in KEGG pathways pertaining to pathogenesis of Qi Stagnation and Blood Stasis- (QS & BS-) & associated diseases such as coronary heart disease and digestive diseases. The expression level of FZD8 was significantly higher in response patients than that in nonresponse patients (p = 0.041) and circRNA_13799 significantly lower in response patients than that in nonresponse patients (p = 0.040) based on real-time PCR. Patients with higher expression level of FZD8 with 75% stratification have significantly higher reduction in the questionnaire score (p = 0.010), and the area under the curve (AUC) was 0.765 (95%CI = 0.593-0.936; p = 0.014).

Conclusions: FZD8 might perform the sensitive biomarker for predicting the effectiveness of XFZYC. However, further prospective cohort study was warranted to confirm the exact specificity and sensitivity of this biomarker.