Methods and compositions for diagnosis of ectopic pregnancy

Abstract

Methods and compositions are provided for diagnosing ectopic pregnancy in a mammalian subject by detecting changes in expression of ISM2, ADAM12, PST1, PSG7, PST11, PSG9, PSG2 and other genes identified therein, including combinations thereof. A selected gene, gene transcript or protein/peptide expression product, or profiles or signatures formed by combinations of same, detected in a biological fluid of a subject, enables comparison of the corresponding genes, proteins or profiles from that of a reference or control having a normal intrauterine pregnancy. Detection of characteristic changes in the gene profile or protein expression signature of the subject is correlated with a diagnosis of ectopic pregnancy. Various compositions for use in such diagnosis include PCR primer-probe sets or ligands, labeled or immobilized, which are capable of detecting the changes in expression or translation of these targets.

1 . A method for diagnosing an ectopic pregnancy in a female mammalian subject comprising:
 (a) measuring in a biological fluid sample of the subject the expression levels of Isthmin2 (ISM2) protein or peptide and one or more proteins or peptides selected from the group consisting of:
 i. the pro-domain or extracellular (EC) domain of ADAM12, 
 ii. pregnancy specific beta-1 glycoprotein isoform 1 (PSG1), 
 iii. pregnancy specific beta-1 glycoprotein isoform 7 (PSG7), 
 iv. pregnancy specific beta-1 glycoprotein isoform 11 (PSG11), 
 v. pregnancy specific beta-1 glycoprotein isoform 9 (PSG9), and 
 vi. pregnancy specific beta-1 glycoprotein isoform 2 (PSG2); 
 wherein the expression level of each said protein or peptide is measured by a ligand which binds to the protein or peptide; and 
   (b) optionally, measuring in said biological fluid sample of the subject the expression level of a protein or peptide selected from the group consisting of:
 vii. choriogonadotropin subunit beta precursor (CGB); 
 viii. glycoprotein hormones alpha chain precursor (CGA); 
 ix. pappalysin-1 precursor (PAPPA); 
 x. chorionic somatomammotropin hormone precursor (CSH1); and 
 xi. progestagen-associated endometrial protein (PAEP); 
 wherein the expression level of each said selected protein or peptide is measured by a ligand which binds to the protein or peptide; and 
   (c) comparing said subject's selected protein or peptide expression levels with the levels of the same protein or peptide in the biological fluid of a reference or control female mammalian subject having a normal intrauterine pregnancy (IUP),   wherein changes in expression of the subject's selected proteins or peptides from those of the reference or control correlates with a diagnosis of ectopic pregnancy.   
     
     
         2 . The method according to  claim 1 , wherein said change in expression level of each said selected protein or peptide comprises an upregulation in comparison to said reference or control or a downregulation in comparison to said reference or control. 
     
     
         3 . The method according to  claim 1 , wherein the ligand is a protein or peptide. 
     
     
         4 . The method according to  claim 1 , wherein the ligand is a polynucleotide or oligonucleotide. 
     
     
         5 . The method according to  claim 1 , wherein the ligand is associated with a detectable label. 
     
     
         6 . The method according to  claim 1 , wherein said polynucleotide or oligonucleotide is part of a primer-probe set, wherein each primer-probe set amplifies a different gene, or gene expression product.