Teng-Fei Yuan1, Shao-Ting Wang1, Juan Le1, Yan Li2. 1. Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China. 2. Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: yanli_1120@163.com.
Abstract
BACKGROUND: Trisomy 21 is a serious chromosome abnormality. The conventional Down's screening test is the most widely used for trisomy 21 screening. However, this method could lead to a higher false positive rate. Therefore, we aim to analyze steroid profile in second-trimester pregnant women and identify novel serum biomarkers of trisomy 21. METHODS: We employed an LC-MS/MS method to measure the steroid profile. The concentrations and product-to-substrate ratios in 71 second-trimester pregnant women were determined and statistically analyzed to identify novel biomarkers for trisomy 21 screening. RESULTS: We found that there were significant differences in levels of E3, 11-deoxycortisol, and 11-deoxycortisol /17-hydroxyprogesterone between two groups. The OPLS-DA plots revealed obvious separation between two groups. Combining VIP analysis (VIP > 1.0) with volcano plot (P < 0.05 and fold change >1.2 or < 0.83), 11-deoxycortisol was identified as a novel biomarker for trisomy 21. After controlling for confounders, we found 11-deoxycortisol was associated with trisomy 21 (adjusted P = 0.009), and the fully adjusted OR (95 % CI) was 0.098 (0.016-0.593) in highest quartile versus lowest quartile of 11-deoxycortisol (P = 0.011). CONCLUSIONS: Steroid profile analysis for the first time showed that steroid hormones perturbations occurred in pregnant women carrying a fetus affected by trisomy 21 and decreased 11-deoxycortisol levels were associated with trisomy 21.
BACKGROUND: Trisomy 21 is a serious chromosome abnormality. The conventional Down's screening test is the most widely used for trisomy 21 screening. However, this method could lead to a higher false positive rate. Therefore, we aim to analyze steroid profile in second-trimester pregnant women and identify novel serum biomarkers of trisomy 21. METHODS: We employed an LC-MS/MS method to measure the steroid profile. The concentrations and product-to-substrate ratios in 71 second-trimester pregnant women were determined and statistically analyzed to identify novel biomarkers for trisomy 21 screening. RESULTS: We found that there were significant differences in levels of E3, 11-deoxycortisol, and 11-deoxycortisol /17-hydroxyprogesterone between two groups. The OPLS-DA plots revealed obvious separation between two groups. Combining VIP analysis (VIP > 1.0) with volcano plot (P < 0.05 and fold change >1.2 or < 0.83), 11-deoxycortisol was identified as a novel biomarker for trisomy 21. After controlling for confounders, we found 11-deoxycortisol was associated with trisomy 21 (adjusted P = 0.009), and the fully adjusted OR (95 % CI) was 0.098 (0.016-0.593) in highest quartile versus lowest quartile of 11-deoxycortisol (P = 0.011). CONCLUSIONS:Steroid profile analysis for the first time showed that steroid hormones perturbations occurred in pregnant women carrying a fetus affected by trisomy 21 and decreased 11-deoxycortisol levels were associated with trisomy 21.