Early Diagnosis Of Epithelial Ovarian Cancer Research Articles

Identification of metabolic biomarkers for diagnosis of epithelial ovarian cancer using internal extraction electrospray ionization mass spectrometry (iEESI-MS).

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies. The poor prognosis of EOC is mainly due to its asymptomatic early stage, lack of effective screening methods, and a late diagnosis in the advanced stages of the disease. This study investigated metabolomic abnormalities in epithelial ovarian cancers. Our study developed a novel strategy to rapidly identify the metabolic biomarkers in the plasma of the EOC patients using Internal Extraction Electrospray Ionization Mass Spectrometry (IEESI-MS) and Liquid Chromatography-mass Spectrometry (HPLC-MS), which could distinguish the differential metabolites in between plasma samples collected from 98 patients with epithelial ovarian cancer, including 78 cases with original (P), and 20 cases with self-configuration (ZP), as well as 60 healthy subjects, including 30 cases in the original sample (H), 30 cases in self-configuration (ZH), and 6 cases in a blind sample (B). Our study detected 880 metabolites based on criteria variable importance in projection (VIP) > 1, among which 26 metabolites were selected for further identification. They are mainly metabolism-related lipids, amino acids, nucleic acids, and others. The metabolic pathways associated with the differential metabolites were explored by the KEGG analysis, a comprehensive database that integrates genome, chemistry, and system function information. The abnormal metabolites of EOC patients identified by IEESI-MS and HPLC-MS included Lysophosphatidylcholine (16:0) [Lyso PC (16:0)], L-Phenylalanine, L-Leucine, Phenylpyruvic acid, L-Tryptophan, and L-Histidine. Identifying the abnormal metabolites of EOC patients through metabolomics analyses could provide a new strategy to identify valuable potential biomarkers for the screening and early diagnosis of EOC.

Abstract B15: A cancer-specific detection of serum CA125 improves differential diagnosis of epithelial ovarian cancer from benign conditions

Abstract Introduction: We have developed an assay that distinguishes CA125 originating from malignant and benign sources. The assay combines conventional immunoassay with the detection of carbohydrates differentially glycosylated in epithelial ovarian cancer (EOC). These glycans can be detected using carbohydrate-reactive lectins. Our recent data showed that CA125 detection using MGL-lectin improves the discrimination of cancerous CA125 from CA125 of endometriosis patients (Gidwani et al., Clin.Chem 2016). The current study extends CA125MGL measurements to a broader sample set and longitudinal collections during EOC treatment and follow-up. Methods: MGL lectin coated onto fluorescent europium-chelate-doped 97-nm nanoparticles was used for detection of the CA125 that was captured on an anti-CA125 antibody immobilized on microtitration wells. Serum samples from high-grade serous EOC or patients with varying benign conditions and healthy controls were analyzed. Results: CA125MGL specifically recognized the CA125 isoform produced by EOC, whereas the recognition of CA125 from nonmalignant conditions was reduced. Serum CA125MGL measurement discriminated better patients with EOC from benign conditions compared with conventional immunoassay. Importantly, discrimination was particularly improved for marginally increased CA125 values that are common in benign conditions. Our data also showed earlier detection of EOC progression, suggesting that the CA125MGL also has potential to improve earlier diagnosis of EOC. Conclusions: The CA125MGL concept could help reduce the false-positive rates of conventional CA125 immunoassays. It carries further potential to improve early diagnosis of EOC as well as follow-up of treatment response. Finally, using appropriate combinations of lectins and antibodies, applying the test concept presented here can also be explored for other diagnostic targets, where changes in glycosylation are indicative of an ongoing disease process. Citation Format: Kaisa Huhtinen, Kamlesh Gidwani, Henna Kekki, Johanna Hynninen, Liina Salminen, Antti Perheentupa, Matti Poutanen, Annika Auranen, Seija Grenman, Urpo Lamminmäki, Olli Carpén, Kim Pettersson. A cancer-specific detection of serum CA125 improves differential diagnosis of epithelial ovarian cancer from benign conditions. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B15.

The significance of RASSF2A promoter methylation in the early diagnosis of epithelial ovarian cancer

Objective To evaluate the methylation status of RASSF2A in epithelial ovarian cancer (EOC) tissues and plasma, and to explore the correlations in two kinds of samples with clinicopathological characteristics. Methods The frequency of methylation of the RASSF2A gene in tissues and corresponding plasma samples from 60 EOC patients, 20 patients with benign ovarian tumors and 10 patients with normal ovarian tissues were detected respectively. The methylation-specific PCR was used to determine the methylation status. Results The frequency of aberrant methylation of RASSF2A was 58.3 % (35/60) in EOC tissues and 43.3 % (26/60) in corresponding plasma samples respectively, however, such hypermethylation was not detected in the benign ovarian tumors and normal ovarian samples, and there was significant difference between them (P 0.05). Conclusions The promoter methylation of RASSF2A gene is an early and frequent epigenetic event in EOC. Detection of promoter hypermethylation in plasma specimens can help the early diagnosis of EOC. Key words: Ovarian neoplasms; Gene, RASSF2A; Serum; Methylation