A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature

被引:446
作者
Diaz-Gimeno, Patricia [1 ,2 ]
Horcajadas, Jose A. [4 ]
Martinez-Conejero, Jose A. [4 ]
Esteban, Francisco J. [3 ]
Alama, Pilar [1 ,2 ]
Pellicer, Antonio [1 ,2 ]
Simon, Carlos [1 ,2 ,5 ]
机构
[1] Univ Valencia, Fdn IVI, Inst Univ IVI, Valencia, Spain
[2] Univ Valencia, Sanitaria Hosp Clin Valencia, Inst Invest, Valencia, Spain
[3] Univ Jaen, Dept Expt Biol, Jaen, Spain
[4] iGenomix, Valencia, Spain
[5] Ctr Invest Principe Felipe, Valencia, Spain
关键词
Endometrial receptivity; endometrial dating; microarray; transcriptomic signature; predictor; diagnostic tool; MOLECULAR CLASSIFICATION; EXPRESSION PROFILES; CLASS PREDICTION; CANDIDATE GENES; CANCER; IMPLANTATION; CHEMOKINES; DISCOVERY; ESTROGEN; TISSUE;
D O I
10.1016/j.fertnstert.2010.04.063
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Objective: To create a genomic tool composed of a customized microarray and a bioinformatic predictor for endometrial dating and to detect pathologies of endometrial origin. To define the transcriptomic signature of human endometrial receptivity. Design: Two cohorts of endometrial samples along the menstrual cycle were used: one to select the genes to be included in the customized microarray (endometrial receptivity array [ERA]), and the other to be analyzed by ERA to train the predictor for endometrial dating and to define the transcriptomic signature. A third cohort including pathological endometrial samples was used to train the predictor for pathological classification. Setting: Healthy oocyte donors and patients. Patient(s): Healthy fertile women (88) and women with implantation failure (5) or hydrosalpinx (2). Intervention(s): Human endometrial biopsies. Main Outcome Measure(s): The gene expression of endometrial biopsies. Result(s): The ERA included 238 selected genes. The transcriptomic signature was defined by 134 genes. The predictor showed a specificity of 0.8857 and sensitivity of 0.99758 for endometrial dating, and a specificity of 0.1571 and a sensitivity of 0.995 for the pathological classification. Conclusion(s): This diagnostic tool can be used clinically in reproductive medicine and gynecology. The transcriptomic signature is a potential endometrial receptivity biomarkers cluster. (Fertil Steril (R) 2011; 95: 50-60. (C)2011 by American Society for Reproductive Medicine.)
引用
收藏
页码:50 / U611
页数:26
相关论文
共 50 条
[1]  
Aghajanova L., 2008, Expert Rev Obstet Gynecol, V3, P487
[2]   BABELOMICS: a suite of web tools for functional annotation and analysis of groups of genes in high-throughput experiments [J].
Al-Shahrour, F ;
Minguez, P ;
Vaquerizas, JM ;
Conde, L ;
Dopazo, J .
NUCLEIC ACIDS RESEARCH, 2005, 33 :W460-W464
[3]   FatiGO:: a web tool for finding significant associations of Gene Ontology terms with groups of genes [J].
Al-Shahrour, F ;
Díaz-Uriarte, R ;
Dopazo, J .
BIOINFORMATICS, 2004, 20 (04) :578-580
[4]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[5]   Multi-platform, multi-site, microarray-based human tumor classification [J].
Bloom, G ;
Yang, IV ;
Boulware, D ;
Kwong, KY ;
Coppola, D ;
Eschrich, S ;
Quackenbush, J ;
Yeatman, TJ .
AMERICAN JOURNAL OF PATHOLOGY, 2004, 164 (01) :9-16
[6]   Determination of the transcript profile of human endometrium [J].
Borthwick, JM ;
Charnock-Jones, DS ;
Tom, BD ;
Hull, ML ;
Teirney, R ;
Phillips, SC ;
Smith, SK .
MOLECULAR HUMAN REPRODUCTION, 2003, 9 (01) :19-33
[7]   Random forests [J].
Breiman, L .
MACHINE LEARNING, 2001, 45 (01) :5-32
[8]   Changes in gene expression during the early to mid-luteal (receptive phase) transition in human endometrium detected by high-density microarray screening [J].
Carson, DD ;
Lagow, E ;
Thathiah, A ;
Al-Shami, R ;
Farach-Carson, MC ;
Vernon, M ;
Yuan, LW ;
Fritz, MA ;
Lessey, B .
MOLECULAR HUMAN REPRODUCTION, 2002, 8 (09) :871-879
[9]   maSigPro:: a method to identify significantly differential expression profiles in time-course microarray experiments [J].
Conesa, A ;
Nueda, MJ ;
Ferrer, A ;
Talón, M .
BIOINFORMATICS, 2006, 22 (09) :1096-1102
[10]   Histological dating of timed endometrial biopsy tissue is not related to fertility status [J].
Coutifaris, C ;
Myers, ER ;
Guzick, DS ;
Diamond, MP ;
Carson, SA ;
Legro, RS ;
McGovern, PG ;
Schlaff, WD ;
Carr, BR ;
Steinkampf, MP ;
Silva, S ;
Vogel, DL ;
Leppert, PC .
FERTILITY AND STERILITY, 2004, 82 (05) :1264-1272