Can biomarkers identified from the uterine fluid transcriptome be used to establish a noninvasive endometrial receptivity prediction tool? A proof-of-concept study.
Can biomarkers identified from the uterine fluid transcriptome be used to establish a noninvasive endometrial receptivity prediction tool? A proof-of-concept study.
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从子宫液体转录组中鉴定出的生物标志物可以用于建立非侵入性子宫内膜容受性预测工具吗？
DOI：
10.1186/s12958-023-01070-0
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发表时间：
2023-02-18
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胚胎植入接受子宫内膜是成功妊娠的关键。基于子宫内膜活检的子宫内膜转录组生物标志物的子宫内膜容受性（ER）预测工具已被用于指导体外受精（IVF）患者成功的胚胎植入。然而，目前尚无可靠的无创ER预测方法，迫切需要一种可靠的无创ER预测方法。我们旨在从子宫液转录组测序数据中识别生物标志物，建立无创ER预测工具，并评估其在体外受精患者中的临床应用潜力。结合随机森林算法，对48例ER正常的IVF患者在3种不同接受状态下的144份子宫液标本（LH + 5、LH + 7、LH + 9）进行转录组学分析，建立基于RNA-seq的无创子宫内膜容受性试验（nirsERT）。随后，我们招募了22例接受冻融囊胚移植的IVF患者，并分析了nirsERT预测结果与妊娠结局的相关性。共有864个er相关差异表达基因（DEGs）参与子宫内膜-胚胎串扰相关的生物学过程，包括蛋白质结合、信号接收和转导、生物大分子运输和细胞-细胞粘附连接。随后，采用随机森林算法建立了由87个标记和3个枢纽基因组成的nirsERT模型。10倍交叉验证平均准确率为93.0%。一个小队列（n = 22）回顾性观察显示，预测WOI正常的IVF患者中77.8%（14/18）成功宫内妊娠，而3例WOI移位的患者均未成功妊娠。1例患者因测序数据质量差而失败。基于子宫液转录组生物标志物的NirsERT可以相对准确地预测WOI周期，可作为生殖诊所无创、可靠的ER同周期检测。中国临床试验注册：ChiCTR-DDD-17013375。2017年11月14日注册，http://www.chictr.org.cn/index.aspx。在线版本包含补充材料，可在10.1186/s12958-023-01070-0获得。
Embryo implantation in a receptive endometrium is crucial for successful pregnancy. Endometrial receptivity (ER) prediction tools based on endometrial transcriptome biomarkers by endometrial biopsy have been used to guide successful embryo implantation in in vitro fertilization (IVF) patients. However, no reliable noninvasive ER prediction method has been established, and one is greatly needed. We aimed to identify biomarkers from uterine fluid transcriptomic sequencing data for establishing noninvasive ER prediction tool and to evaluate its clinical application potential in patients undergoing IVF. The non-invasive RNA-seq based endometrial receptivity test (nirsERT) was established by analyzing transcriptomic profile of 144 uterine fluid specimens (LH + 5, LH + 7, and LH + 9) at three different receptive status from 48 IVF patients with normal ER in combination with random forest algorithm. Subsequently, 22 IVF patients who underwent frozen-thaw blastocyst transfer were recruited and analyzed the correlation between the predicted results of nirsERT and pregnancy outcomes. A total of 864 ER-associated differentially expressed genes (DEGs) involved in biological processes associated with endometrium-embryo crosstalk, including protein binding, signal reception and transduction, biomacromolecule transport and cell-cell adherens junctions, were selected. Subsequently, a nirsERT model consisting of 87 markers and 3 hub genes was established using a random forest algorithm. 10-fold cross-validation resulted in a mean accuracy of 93.0%. A small cohort (n = 22) retrospective observation shows that 77.8% (14/18) of IVF patients predicted with a normal WOI had successful intrauterine pregnancies, while none of the 3 patients with a displaced WOI had successful pregnancies. One patient failed due to poor sequencing data quality. NirsERT based on uterine fluid transcriptome biomarkers can predict the WOI period relatively accurately and may serve as a noninvasive, reliable and same cycle test for ER in reproductive clinics. Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx. The online version contains supplementary material available at 10.1186/s12958-023-01070-0.
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DOI：
10.1093/bioinformatics/bts251
发表时间：
2012-07-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Jiao X;Sherman BT;Huang da W;Stephens R;Baseler MW;Lane HC;Lempicki RA
通讯作者：
Lempicki RA
影响因子：
6.7
作者：
Garrido-Gomez, Tamara;Ruiz-Alonso, Maria;Simon, Carlos
通讯作者：
Simon, Carlos
影响因子：
6.7
作者：
Coutifaris, C;Myers, ER;Leppert, PC
通讯作者：
Leppert, PC
hCG 触发后子宫内膜回声模式转变在预测 IVF 妊娠结局中的价值：一项前瞻性队列研究
影响因子：
4.4
作者：
Hou, Zhaojuan;Zhang, Qiong;Li, Yanping
通讯作者：
Li, Yanping
影响因子：
--
作者：
Nagalakshmi, Ugrappa;Waern, Karl;Snyder, Michael
通讯作者：
Snyder, Michael