scholarly journals Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer

2022 ◽  
Author(s):  
Trasias Mukama ◽  
Renée Turzanski Fortner ◽  
Verena Katzke ◽  
Lucas Cory Hynes ◽  
Agnese Petrera ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Serum Levels ◽  
Lag Time ◽  
Protein Biomarkers ◽  
Serum Samples ◽  
Good Discrimination ◽  
Diagnostic Biomarkers ◽  
Novel Biomarkers ◽  
Prospective Investigation

Abstract Background CA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer. Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer. Results Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancer-free. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9–18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone. Conclusion Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0–9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125.

scholarly journals Automated Assay of a Four-Protein Biomarker Panel for Improved Detection of Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 325
Author(s):  
Christopher Walker ◽  
Tuan-Minh Nguyen ◽  
Shlomit Jessel ◽  
Ayesha B. Alvero ◽  
Dan-Arin Silasi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Predictive Value ◽  
Early Stage ◽  
Ca 125 ◽  
Healthy Controls ◽  
Classification Models ◽  
Serum Samples ◽  
Protein Biomarker ◽  
Biomarker Panel

Background: Mortality from ovarian cancer remains high due to the lack of methods for early detection. The difficulty lies in the low prevalence of the disease necessitating a significantly high specificity and positive-predictive value (PPV) to avoid unneeded and invasive intervention. Currently, cancer antigen- 125 (CA-125) is the most commonly used biomarker for the early detection of ovarian cancer. In this study we determine the value of combining macrophage migration inhibitory factor (MIF), osteopontin (OPN), and prolactin (PROL) with CA-125 in the detection of ovarian cancer serum samples from healthy controls. Materials and Methods: A total of 432 serum samples were included in this study. 153 samples were from ovarian cancer patients and 279 samples were from age-matched healthy controls. The four proteins were quantified using a fully automated, multi-analyte immunoassay. The serum samples were divided into training and testing datasets and analyzed using four classification models to calculate accuracy, sensitivity, specificity, PPV, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Results: The four-protein biomarker panel yielded an average accuracy of 91% compared to 85% using CA-125 alone across four classification models (p = 3.224 × 10−9). Further, in our cohort, the four-protein biomarker panel demonstrated a higher sensitivity (median of 76%), specificity (median of 98%), PPV (median of 91.5%), and NPV (median of 92%), compared to CA-125 alone. The performance of the four-protein biomarker remained better than CA-125 alone even in experiments comparing early stage (Stage I and Stage II) ovarian cancer to healthy controls. Conclusions: Combining MIF, OPN, PROL, and CA-125 can better differentiate ovarian cancer from healthy controls compared to CA-125 alone.

scholarly journals Serum Vascular Endothelial Growth Factor VEGF and Interlukin-8 As a Novel Biomarkers For Early Detection of Ovarian Tumors

2015 ◽  
Vol 12 (2) ◽  
pp. 293-300
Author(s):  
Baghdad Science Journal
Keyword(s):  
Ovarian Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Serum Levels ◽  
Elisa Test ◽  
Ovarian Tumors ◽  
Benign Tumors ◽  
Vascular Endothelial ◽  
Additional Tool ◽  
Novel Biomarkers ◽  
Endothelial Growth Factor

Epithelial ovarian cancer is the leading cause of cancer deaths from gynecological malignancies. Angiogenesis is considered essential for tumor growth and the development of metastases. VEGF and IL?8 are potent angiostimulatory molecules and their expression has been demonstrated in many solid tumors, including ovarian cancer.VEGF and IL-8 concentrations were measured by ELISA test (HumanVEGF,IL-8). Bioassay ELISA/ US Biological / USA).The median VEGF and IL-8 levels were significantly higher in the sera of ovarian cancer patients than in those with benign tumors and in healthy controls.Pretreatment VEGF and IL-8 serum levels might be regarded as an additional tool in the differentiation of ovarian tumors.

Proteomic analysis for early detection of ovarian cancer: A realistic approach?

2003 ◽  
Vol 13 (Suppl 2) ◽  
pp. 133-139 ◽  
Author(s):  
E. V. Stevens ◽  
L. A. Liotta ◽  
E. C. Kohn
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Serum Protein ◽  
Mass Spectroscopy ◽  
Biomarker Discovery ◽  
Protein Pattern ◽  
Protein Biomarkers ◽  
Promising Tool ◽  
Chip Technology ◽  
Stage Disease

Ovarian cancer is a multifaceted disease wherein most women are diagnosed with advanced stage disease. One of the most imperative issues in ovarian cancer is early detection. Biomarkers that allow cancer detection at stage I, a time when the disease is amenable to surgical and chemotherapeutic cure in over 90% of patients, can dramatically alter the horizon for women with this disease. Recent developments in mass spectroscopy and protein chip technology coupled with bioinformatics have been applied to biomarker discovery. The complexity of the proteome is a rich resource from which the patterns can be gleaned; the pattern rather than its component parts is the diagnostic. Serum is a key source of putative protein biomarkers, and, by its nature, can reflect organ-confined events. Pioneering use of mass spectroscopy coupled with bioinformatics has been demonstrated as being capable of distinguishing serum protein pattern signatures of ovarian cancer in patients with early- and late-stage disease. This is a sensitive, precise, and promising tool for which further validation is needed to confirm that ovarian cancer serum protein signature patterns can be a robust biomarker approach for ovarian cancer diagnosis, yielding improved patient outcome and reducing the death and suffering from ovarian cancer.

Gonadotropin Levels in Ovarian Cyst Fluids: A Predictor of Malignancy?

1998 ◽  
Vol 13 (3) ◽  
pp. 165-168 ◽  
Author(s):  
S. Krämer ◽  
M. Leeker ◽  
W. Jäger
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Elevated Serum ◽  
Serum Levels ◽  
Ovarian Tumors ◽  
Surgical Removal ◽  
Serum Samples ◽  
Benign Ovarian Tumors ◽  
Surprising Finding ◽  
Cyst Fluids

Gonadotropins can stimulate ovarian cancer growth in cell cultures. Corresponding LH/hCG receptors have been demonstrated in ovarian cancer. However, reduction of elevated serum gonadotropins by GnRH analogs in ovarian cancer patients did not lead to growth restriction, which means that serum levels of gonadotropins may not play the most important role in ovarian cancer. We therefore analyzed the LH and FSH concentrations in cyst fluids of ovarian cancer. Patients with preoperatively diagnosed cystic ovarian tumors were eligible for the study. Serum samples of the patients were obtained during surgery, while the fluids within the cysts were aspirated after surgical removal of the tumor. FSH and LH levels in serum and cyst fluids were measured using single antibody EIA (Boehringer Mannheim GmbH, Germany). Cyst fluids and sera of 108 patients were evaluated. While there were no significant differences in the FSH and LH serum concentrations, highly significant differences in the FSH and LH levels in cyst fluids were found. Only cancer cysts contained FSH and LH, while the corresponding concentrations in benign cysts were always below the measuring range of the assays. This clear division between high gonadotropin levels in cysts of serous ovarian cancer and low or absent concentrations in benign ovarian tumors further supports the hypothesis that FSH and LH may play a role in ovarian cancer; however, explanations for this surprising finding are still lacking.

scholarly journals Value of [18F]FDG-PET/CT and CA125, serum levels and kinetic parameters, in early detection of ovarian cancer recurrence

Medicine ◽  
2018 ◽  
Vol 97 (17) ◽  
pp. e0098 ◽  
Author(s):  
Azahara Palomar Muñoz ◽  
José Manuel Cordero García ◽  
Mª del Prado Talavera Rubio ◽  
Ana Mª García Vicente ◽  
Francisco José Pena Pardo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Kinetic Parameters ◽  
Fdg Pet ◽  
Cancer Recurrence ◽  
Serum Levels ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

scholarly journals Identification of a Novel Biomarker for Biliary Tract Cancer Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Shintaro Kikkawa ◽  
Kazuyuki Sogawa ◽  
Mamoru Satoh ◽  
Hiroshi Umemura ◽  
Yoshio Kodera ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Serum Levels ◽  
Stage I ◽  
Characteristic Analysis ◽  
Serum Samples ◽  
Ionization Time ◽  
Tract Cancer ◽  
Flight Mass Spectrometry ◽  
Novel Biomarkers

Early diagnosis of biliary tract cancer (BTC) is important for curative surgical resection. Current tumor markers of BTC are unsatisfactory in terms of sensitivity and specificity. In a search for novel biomarkers for BTC, serum samples obtained from 62 patients with BTC were compared with those from patients with benign biliary diseases and from healthy controls, using the MALDI-TOF/TOF ClinProt system. Initial screening and further validation identified a peak at 4204 Da with significantly greater intensity in the BTC samples. The 4204 Da peak was partially purified and identified as a fragment of prothrombin by amino acid sequencing. The sensitivity of the 4204 Da peptide for detection of stage I BTC cancer was greater than those for CEA and CA19-9. Also, serum levels of the 4204 Da peptide were above the cut-off level in 15 (79%) of 19 cases in which the CEA and CA19-9 levels were both within their cut-off values. Receiver operating characteristic analysis showed that the combination of the 4204 Da peptide and CA19-9 was significantly more sensitive for detection of stage I BTC cancer compared to CEA and CA19-9. These results suggest that this protein fragment may be a promising biomarker for biliary tract cancer.

Performance of a biomarker panel to identify malignancy within a pelvic mass population

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5566-5566
Author(s):  
L. Chen ◽  
H. D. Homesley ◽  
D. R. Scribner ◽  
G. H. Cantuaria ◽  
Q. He ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Differential Diagnosis ◽  
Early Stage ◽  
Pelvic Mass ◽  
Stage Iv ◽  
Serum Levels ◽  
Borderline Tumor ◽  
Serum Samples ◽  
Early Stage Disease ◽  
Biomarker Analysis

5566 Background: We previously reported the performance of biomarker combinations that displayed utility in identifying ovarian cancer from normal sera and in monitoring for disease recurrence. In this study, we evaluated the performance of a subset of these markers in differentiating ovarian cancer from benign pelvic mass. Methods: Pre-operative serum samples were prospectively collected from 254 patients undergoing surgical evaluation for differential diagnosis of a pelvic mass. Pathology showed 76 cases of epithelial ovarian carcinoma (EOC), 17 borderline tumors, 11 other gynecologic cancers, and 150 benign masses. 18 (23.7%) of the EOC patients had stage I tumors; 6 (7.9%) stage II; 44 (57.9%) stage III; and 8 (10.5%) stage IV. Serum levels of CA125, HE4, glycodelin, SLPI, MMP7, and Plau-R were ascertained. Biomarker performance was evaluated by a logistic regression model and leave one out cross-validation analysis. All calculations compared the benign vs. EOC and borderline tumor populations. Results: Individual biomarker sensitivity ranged from 28% to 77% at 85% specificity. The combination of CA125, HE4 and glycodelin exhibited the highest overall performance in identifying malignancy from benign masses, demonstrating 80% sensitivity, 80% specificity in patients <55 years, and 89% sensitivity, 80% specificity in patients ≥55. Total cohort performance was 85% sensitivity and 80% specificity. Glycodelin identified 7/22 CA125 and HE4 double negative patients, 5/7 of these patients were early stage (borderline, I or II), while only adding 4/150 false positive cases. Conclusions: Biomarker analysis within this test cohort demonstrates potential clinical utility in the differential diagnosis of pelvic mass patients, especially for the detection of early stage disease. The addition of glycodelin improved the detection of early stage cancer in sera that were negative for both HE4 and CA125. [Table: see text]

Circulating exosomal microRNAs as novel detection biomarkers in pancreatic cancer

2020 ◽  
Author(s):  
Lun Wu(Former Corresponding Author) ◽  
Wen-Bo Zhou ◽  
Jiao Zhou ◽  
Ying Wei ◽  
Hong-Mei Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Rna Isolation ◽  
Serum Levels ◽  
Tumor Stage ◽  
Serum Samples ◽  
Expression Levels ◽  
Transmission Electron ◽  
Significant Difference ◽  
Novel Biomarkers ◽  
Exosomal Mirna

Abstract Background Circulating exosomal microRNAs are reflective of the characteristics of the tumor, are valuable biomarkers in different types of tumors, and play important roles in tumor progression and metastasis. The purpose of this study was to investigate the circulating exosomal microRNAs miRNA-21 and miRNA-210 as novel biomarkers for patients with pancreatic cancer (PC).Methods Serum exosomal microRNAs were extracted from the serum of PC and chronic pancreatitis (CP) patients using an RNA Isolation kit. To identify the exosomes in the serum, we used transmission electron micrographs for the crystalline structure, western blotting, and NanoSight for exosomal markers and nanoparticle characterization. The relative expression levels of exosomal microRNAs were quantified using quantitative PCR and compared between PC and CP patients.Results A total of 40 serum samples (30 PC and 10 CP) were collected. The expression levels of both exosomal miRNA-21 and miRNA-210 were obviously higher in PC patients compared with those in CP patients (both P<0.001). However, no significant difference in the relative serum levels of free miR-21 and miR-210 was observed between these two groups (both P>0.05). Exosomal miRNA-21 and miRNA-210 were related to tumor stage, as well as other factors. The diagnostic of exosomal miRNA-21 and miRNA-210 levels was 83% and 85%, respectively. Furthermore, when combining the expression of exosomal miRNA with serum CA19-9, the accuracy increased to 90%.Conclusions We herein identified that the serum exosomal miRNAs miRNA-21 and miRNA-210 may be of value as potential biomarkers and therapeutic targets for the diagnosis and treatment of PC.

Identification of Treponema pallidum–specific protein biomarkers in syphilis patient serum using mass spectrometry

2021 ◽  
Author(s):  
Man-Li Tong ◽  
Dan Liu ◽  
Li-Li Liu ◽  
Li-Rong Lin ◽  
Hui-Lin Zhang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Treponema Pallidum ◽  
Specific Protein ◽  
Protein Biomarkers ◽  
Serum Samples ◽  
Disease Outcomes ◽  
Before And After ◽  
Novel Biomarkers

Aim: To screen novel biomarkers in serum of syphilis patients using a mass spectrometry-based method. Materials & methods: Sera were collected from 18 syphilis patients and divided into three groups. Every six serum samples (before and after treatment) in each group were pooled and detected by mass spectrometry. Results: Twenty-five unique peptides corresponding to 15 Treponema pallidum proteins were discovered. Among them, Tp0369 was discovered as a promising biomarker candidate in this study. Tp0524 and Tp0984 levels decreased 0.38-fold and 0.51-fold after BPG treatment, respectively, which may be related to disease outcomes of syphilis. Conclusion: These findings confirmed the presence of detectable T. pallidum protein in patients' serum, which could promote the development of syphilis diagnostics.

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