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Abstract：
BACKGROUND: Despite extensive research, the identification of effective biomarkers for early prediction of preterm birth (PTB) continues to be a challenging endeavor. This study aims to identify amniotic fluid (AF) protein biomarkers useful for the early diagnosis of PTB.
METHODS: We initially identified the protein expression profiles in the AF of women with PTB (n = 22) and full-term birth (FTB, n = 22), from the First People\'s Hospital of Yunnan Province who underwent amniocentesis from November 2019 to February 2020, using mass spectrometry employing the data-independent acquisition (DIA) technique, and then analyzed differentially expressed proteins (DEPs). Subsequently, the least absolute shrinkage and selection operator (LASSO) and random forest analysis were employed to further screen the key proteins for PTB biomarker identification. The receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analyses (DCA) were utilized to assess the discrimination and calibration of the key biomarkers.
RESULTS: A total of 25 DEPs were identified between the PTB and FTB groups, comprising 13 up-regulated and 12 down-regulated proteins. Three key protein biomarkers for early PTB diagnosis were identified: IL1RL1 (interleukin-1 receptor-like 1), APOE (apolipoprotein E), and NECTIN4 (nectin cell adhesion molecule 4). The results of the ROC analysis showed that the area under the curve (AUC) of the three proteins combined as a biomarker for early diagnosis of PTB was 0.913 (95% CI: 0.823-1.000), with a sensitivity of 0.864 and a specificity of 0.955, both superior to those of the individual biomarkers. Bootstrap internal validation revealed a concordance index (C-index) of 0.878, with a sensitivity of 0.812 and a specificity of 0.773, indicating the robust predictive performance of these biomarkers.
CONCLUSIONS: We identified three previously unexplored yet potentially useful protein biomarkers in AF for early PTB diagnosis: IL1RL1, APOE, and NECTIN4.
METHODS: We initially identified the protein expression profiles in the AF of women with PTB (n = 22) and full-term birth (FTB, n = 22), from the First People\'s Hospital of Yunnan Province who underwent amniocentesis from November 2019 to February 2020, using mass spectrometry employing the data-independent acquisition (DIA) technique, and then analyzed differentially expressed proteins (DEPs). Subsequently, the least absolute shrinkage and selection operator (LASSO) and random forest analysis were employed to further screen the key proteins for PTB biomarker identification. The receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analyses (DCA) were utilized to assess the discrimination and calibration of the key biomarkers.
RESULTS: A total of 25 DEPs were identified between the PTB and FTB groups, comprising 13 up-regulated and 12 down-regulated proteins. Three key protein biomarkers for early PTB diagnosis were identified: IL1RL1 (interleukin-1 receptor-like 1), APOE (apolipoprotein E), and NECTIN4 (nectin cell adhesion molecule 4). The results of the ROC analysis showed that the area under the curve (AUC) of the three proteins combined as a biomarker for early diagnosis of PTB was 0.913 (95% CI: 0.823-1.000), with a sensitivity of 0.864 and a specificity of 0.955, both superior to those of the individual biomarkers. Bootstrap internal validation revealed a concordance index (C-index) of 0.878, with a sensitivity of 0.812 and a specificity of 0.773, indicating the robust predictive performance of these biomarkers.
CONCLUSIONS: We identified three previously unexplored yet potentially useful protein biomarkers in AF for early PTB diagnosis: IL1RL1, APOE, and NECTIN4.
摘要：
背景：尽管进行了广泛的研究，识别用于早期预测早产(PTB)的有效生物标志物仍然是一项具有挑战性的工作.本研究旨在鉴定对PTB的早期诊断有用的羊水（AF）蛋白生物标志物。
方法：我们最初确定了PTB（n=22）和足月分娩（FTB，n=22),来自云南省第一人民医院，于2019年11月至2020年2月进行了羊膜穿刺术，使用采用数据无关采集（DIA）技术的质谱，然后分析差异表达蛋白（DEP）。随后，采用最小绝对收缩和选择算子(LASSO)和随机森林分析进一步筛选PTB生物标志物鉴定的关键蛋白.接收机工作特性(ROC)分析,校准图,和决策曲线分析(DCA)用于评估关键生物标志物的鉴别和校准.
结果：在PTB组和FTB组之间总共确定了25个DEP，包括13个上调和12个下调的蛋白质。确定了早期PTB诊断的三个关键蛋白质生物标志物：IL1RL1（白介素-1受体样1），APOE（载脂蛋白E），和NECTIN4（坏死素细胞粘附分子4）。ROC分析结果显示,三种蛋白联合作为PTB早期诊断生物标志物的曲线下面积(AUC)为0.913(95%CI:0.823-1.000),灵敏度为0.864，特异性为0.955，均优于单个生物标志物。Bootstrap内部验证显示一致性指数（C指数）为0.878，灵敏度为0.812，特异性为0.773，表明这些生物标志物具有强大的预测性能。
结论：我们确定了三种以前未探索但潜在有用的蛋白生物标志物用于房颤早期PTB诊断：IL1RL1、APOE、和NECTIN4。
方法：我们最初确定了PTB（n=22）和足月分娩（FTB，n=22),来自云南省第一人民医院，于2019年11月至2020年2月进行了羊膜穿刺术，使用采用数据无关采集（DIA）技术的质谱，然后分析差异表达蛋白（DEP）。随后，采用最小绝对收缩和选择算子(LASSO)和随机森林分析进一步筛选PTB生物标志物鉴定的关键蛋白.接收机工作特性(ROC)分析,校准图,和决策曲线分析(DCA)用于评估关键生物标志物的鉴别和校准.
结果：在PTB组和FTB组之间总共确定了25个DEP，包括13个上调和12个下调的蛋白质。确定了早期PTB诊断的三个关键蛋白质生物标志物：IL1RL1（白介素-1受体样1），APOE（载脂蛋白E），和NECTIN4（坏死素细胞粘附分子4）。ROC分析结果显示,三种蛋白联合作为PTB早期诊断生物标志物的曲线下面积(AUC)为0.913(95%CI:0.823-1.000),灵敏度为0.864，特异性为0.955，均优于单个生物标志物。Bootstrap内部验证显示一致性指数（C指数）为0.878，灵敏度为0.812，特异性为0.773，表明这些生物标志物具有强大的预测性能。
结论：我们确定了三种以前未探索但潜在有用的蛋白生物标志物用于房颤早期PTB诊断：IL1RL1、APOE、和NECTIN4。
