Microheterogeneity of transthyretin in serum and ascitic fluid of ovarian cancer patientsReport as inadecuate




Microheterogeneity of transthyretin in serum and ascitic fluid of ovarian cancer patients - Download this document for free, or read online. Document in PDF available to download.

BMC Cancer

, 5:133

First Online: 17 October 2005Received: 06 April 2005Accepted: 17 October 2005DOI: 10.1186-1471-2407-5-133

Cite this article as: Gericke, B., Raila, J., Sehouli, J. et al. BMC Cancer 2005 5: 133. doi:10.1186-1471-2407-5-133

Abstract

BackgroundTransthyretin TTR, a traditional biomarker for nutritional and inflammatory status exists in different molecular variants of yet unknown importance. A truncated form of TTR has recently been described to be part of a set of biomarkers for the diagnosis of ovarian cancer. The main aim of the study was therefore to characterize differences in microheterogeneity between ascitic fluid and plasma of women affected with ovarian cancer and to evaluate the tumor site as the possible source of TTR.

MethodsSubjects were 48 women with primary invasive epithelial ovarian cancer or recurrent ovarian carcinoma. The control group consisted of 20 postmenopausal women. TTR and retinol-binding protein RBP levels were measured by enzyme-linked immunoassay ELISA and C-reactive protein CRP levels by a high-sensitivity latex particle turbidimetric assay. The molecular heterogeneity of TTR was analysed using immunoprecipitation and matrix-associated laser desorption ionization time-of-flight mass spectrometry MALDI-TOF-MS. Presence of TTR in tumor tissue was determined with indirect peroxidase immunostaining.

ResultsTTR and RBP μg-ml levels in serum were 148.5 ± 96.7 and 22.5 ± 14.8 in affected women compared to 363.3 ± 105.5 and 55.8 ± 9.3 in healthy postmenopausal women p < 0.01. In ascitic fluid, levels were 1.02 ± 0.24 and 4.63 ± 1.57 μg-ml, respectively. The mean levels of TTR and RBP in serum showed a tendency to decrease with the severity of the disease and were lower in affected women whose CRP levels were > 40 mg-ml p = 0.08 for TTR; p < 0.05 for RBP. No differences in TTR microheterogeneity were observed between TTR isolated from serum of affected and healthy women or from ascitic fluid. TTR occurred rather consistently in four variants. Mass signals were at 13758 ± 7, 13876 ± 13 greatest intensity, 13924 ± 21 and 14062 ± 24 Da, representing native, S-cysteinylated, S-cysteinglycinylated and glutathionylated TTR, respectively. Serum of healthy and affected women as well as ascitic fluid contained the truncated fragment of TTR 12828 ± 11 Da. No immunoreactive TTR was observed in the tumor sites.

ConclusionThe severity of the cancer associated catabolism as well as the inflammation status affect serum TTR and RBP levels. Neither TTR nor its truncated form originates from tumor tissue and its occurrence in ascites may well reflect the filtration from blood into ascitic fluid.

List of abbreviations usedBSAbovine serum albumin

CA125cancer associated antigen 125

CRPC-reactive protein

Cys solt cysteine residue on position 10 of each TTR subunit

DaDalton

DTTdithioretiol

EAMenergy-absorbing molecule

ELISAenzyme-linked immunoassay

FIGOInternational Federation of Gynecology and Obstertrics

MALDImatrix assisted laser desorption and ionization – time-of-flight – mass spectrometry

MWmolecular weight

RBPretinol-binding protein

SDstandard deviation

TBSTris-buffered saline

TOCTumor Bank Ovarian Cancer

TTRtransthyretin

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-5-133 contains supplementary material, which is available to authorized users.

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Author: Beate Gericke - Jens Raila - Jalid Sehouli - Sophie Haebel - Dominique Könsgen - Alexander Mustea - Florian J Schweigert

Source: https://link.springer.com/







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