title: Plasma kisspeptin is raised in patients with gestational trophoblastic neoplasia and falls during treatment.
abstract: Kisspeptin is a 54-amino acid peptide, encoded by the anti-metastasis gene KiSS-1, that activates G protein-coupled receptor 54 (GPR54). The kisspeptin-GPR54 system is critical to normal reproductive development. KiSS-1 gene expression is increased in the human placenta in normal and molar pregnancies. Circulating kisspeptin is dramatically increased in normal pregnancy, but levels in GTN have not previously been reported. The present study was designed to determine whether plasma kisspeptin levels are altered in patients with malignant GTN. Thirty-nine blood samples were taken from 11 patients with malignant GTN at presentation during and after chemotherapy. Blood was also sampled from nonpregnant and pregnant volunteers. Plasma kisspeptin IR and hCG concentrations were measured. Plasma kisspeptin IR concentration in nonpregnant (n = 16) females was <2 pmol/l. Plasma kisspeptin IR in females was 803 +/- 125 pmol/l in the first trimester of pregnancy (n = 13), 2,483 +/- 302 pmol/l in the third trimester of pregnancy (n = 7), and <2 pmol/l on day 15 postpartum (n = 7). Plasma kisspeptin IR and hCG concentrations in patients with malignant GTN were elevated at presentation and fell during and after treatment with chemotherapy in each patient (mean plasma kisspeptin IR: prechemotherapy 1,363 +/- 1,076 pmol/l vs. post-chemotherapy <2 pmol/l, P < 0.0001; mean plasma hCG: prechemotherapy 227,191 +/- 152,354 U/l vs. postchemotherapy 2 U/l, P < 0.0001). Plasma kisspeptin IR strongly positively correlated with plasma hCG levels (r(2) = 0.99, P < 0.0001). Our results suggest that measurement of plasma kisspeptin IR may be a novel tumor marker in patients with malignant GTN.
authors.affiliation: Department of Metabolic Medicine, Hammersmith Hospital, Imperial College London, London, W12 ONN, UK.
authors.forename: Waljit S
authors.initials: WS
authors.lastname: Dhillo
authors.forename: Philip
authors.initials: P
authors.lastname: Savage
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Murphy
authors.forename: Owais B
authors.initials: OB
authors.lastname: Chaudhri
authors.forename: Michael
authors.initials: M
authors.lastname: Patterson
authors.forename: Gurjinder M
authors.initials: GM
authors.lastname: Nijher
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Foggo
authors.forename: Garin S
authors.initials: GS
authors.lastname: Dancey
authors.forename: Hugh
authors.initials: H
authors.lastname: Mitchell
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Seckl
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D006063:Chorionic Gonadotropin / Q000097:blood; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D059648:Kisspeptins; D011247:Pregnancy; D014328:Trophoblastic Neoplasms / Q000097:blood* / Q000188:drug therapy; D025521:Tumor Suppressor Proteins / Q000097:blood*; D014594:Uterine Neoplasms / Q000097:blood* / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; C106628:KISS1 protein, human; D059648:Kisspeptins; D025521:Tumor Suppressor Proteins