Detection of novel biomarkers for ovarian cancer with an optical nanotechnology detection system enabling label-free diagnostics

Abstract Circulating tumor cell (CTC) is commonly used as biomarker for early detection, prognostication, decision making, and evaluation of the therapeutic efficacy in cancer treatment. Unfortunately, the poor reproducibility and limited sensitivity with the CTC detection have limited its potential impact on clinical management. A reliable automated CTC detection system is therefore needed. We have designed an automated microfluidic chip-based CTC detection system consisting of three main parts: V-BioChip, Cell RevealTM enrichment and staining system, and an automatic scanning and locating system. We hypothesized this novel system can reliably detect CTC from clinical specimens. SKOV3 ovarian cancer cell line was used first to test the reliability of our system. Ten healthy volunteers, 5 patients with benign ovarian tumors, and 8 patients with epithelial ovarian cancer (EOC) were recruited after obtaining written consents to validate the CTC capturing efficacy in the peripheral blood. The capture rates for spiking test in SKOV3 cells were as 48.3% and 89.6% using EpCAM antibody alone and a combined EpCAM antibody and N-cadherin antibody, respectively. The system was sensitive to detection of low cell count and showed a linear relationship with the cell counts in our test range. The sensitivity and specificity were 62.5% and 100% when CTC was used as a biomarker for EOC. Our results demonstrated that this automatic CTC platform has a high capture rate and is feasible for detection of CTCs in EOC.

Download Full-text

Overexpression of centromere protein K (CENPK) in ovarian cancer is correlated with poor patient survival and associated with predictive and prognostic relevance

PeerJ ◽

10.7717/peerj.1386 ◽

2015 ◽

Vol 3 ◽

pp. e1386 ◽

Cited By ~ 9

Author(s):

Yi-Chao Lee ◽

Chi-Chen Huang ◽

Ding-Yen Lin ◽

Wen-Chang Chang ◽

Kuen-Haur Lee

Keyword(s):

Ovarian Cancer ◽

High Reliability ◽

Ovarian Cancer Cells ◽

Cancer Antigen 125 ◽

Centromere Protein ◽

Novel Biomarkers ◽

Cure Rates ◽

Cancer Tissues ◽

First Time

Ovarian cancer has a poor prognosis. Most patients are diagnosed with ovarian cancer when the disease has reached an advanced stage and cure rates are generally under 30%. Hence, early diagnosis of ovarian cancer is the best means to control the disease in the long term and abate mortality. So far, cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) are the gold-standard tumor markers for ovarian cancer; however, these two markers can be elevated in a number of conditions unrelated to ovarian cancer, resulting in decreased specifically and positive predictive value. Therefore, it is urgent to identify novel biomarkers with high reliability and sensitivity for ovarian cancer. In this study for the first time, we identified a member of the centromere protein (CENP) family, CENPK, which was specifically upregulated in ovarian cancer tissues and cell lines and the overexpression of which was associated with poor prognoses in patients with ovarian cancer. In addition, the presence of CENPK significantly improved the sensitivity of CA125 or HE4 for predicting clinical outcomes of ovarian cancer patients. In conclusion, we identified that CENPK was specifically upregulated in ovarian cancer cells and can be used as a novel tumor marker of ovarian cancer.

Download Full-text

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

Baghdad Science Journal ◽

10.21123/bsj.12.2.293-300 ◽

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.

Download Full-text

Characterisation of Antibodies Against the Active Conformation of Gαi1 Using the SRU-BIND® Label-Free Detection System

Label-Free Technologies for Drug Discovery ◽

10.1002/9780470979129.ch17 ◽

2011 ◽

pp. 255-268

Author(s):

Melanie Leveridge ◽

Chun-Wa Chung ◽

Trevor Wattam

Keyword(s):

Detection System ◽

Active Conformation ◽

Label Free ◽

Label Free Detection

Download Full-text

Monitoring the effects of chemical stimuli on live cells with metasurface-enhanced infrared reflection spectroscopy

10.1101/2021.06.30.450584 ◽

2021 ◽

Author(s):

Steven H. Huang ◽

Jiaruo Li ◽

Zhiyuan Fan ◽

Robert Delgado ◽

Gennady Shvets

Keyword(s):

Intracellular Signaling ◽

Strong Field ◽

Detection System ◽

Field Enhancement ◽

Chemical Imaging ◽

Live Cells ◽

Label Free ◽

Reflection Spectroscopy ◽

Infrared Reflection ◽

Infrared Reflection Spectroscopy

Infrared spectroscopy has found wide applications in the analysis of biological materials. A more recent development is the use of engineered nanostructures, or plasmonic metasurfaces, as substrates for metasurface-enhanced infrared reflection spectroscopy (MEIRS). Here, we demonstrate that strong field enhancement from plasmonic metasurfaces enables the use of MEIRS as a highly informative analytic technique for real-time monitoring of cells. By exposing live cells cultured on a plasmonic metasurface to chemical compounds, we show that MEIRS can be used as a label-free phenotypic assay for detecting multiple cellular responses to external stimuli: changes in cell morphology, adhesion, lipid composition of the cellular membrane, as well as intracellular signaling. Using a focal plane array detection system, we show that MEIRS also enables spectro-chemical imaging at the single-cell level. The described metasurface-based all-optical sensor opens the way to a scalable, high-throughput spectroscopic assay for live cells.

Download Full-text

Identifying Potential Markers for Monitoring Progression to Ovarian Cancer Using Plasma Label-free Proteomics

10.21203/rs.2.19189/v1 ◽

2019 ◽

Author(s):

Wenjie Wang ◽

Hongyu Xie ◽

Bairong Xia ◽

LiuChao Zhang ◽

Ce Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Plasma Protein ◽

Late Stage ◽

Early Stage ◽

Label Free ◽

Absolute Quantitation ◽

Keywords Ovarian Cancer ◽

Benign Ovarian Tumor ◽

Increased Risk

Abstract PurposeCancer antigen 125 (CA125) is considered to have high sensitivity but poor specificity for ovarian cancer. New biomarkers utilized to early detect and monitor the progression of ovarian cancer patients are critically needed. Methods A total of 80 patients including 16 early stage, and matched with 17 late stage, 23 benign ovarian tumor (BOT) and 24 uterine fibroid (UF) patients were utilized to perform plasma proteomics analysis using isobaric tag for relative and absolute quantitation (iTRAQ) method to identify differential diagnostic proteins of ovarian cancer patients. A validation set of 9 early stage, 11 late stage, 17 BOT and 16 UF collected by an independent cohort of samples with the same matching principles was examined to confirm the expressed levels of differential expression proteins by ELISA analysis. Results CRP and ARHGEF 11 were identified as potential diagnostic biomarkers of ovarian cancer. Results of area under the curve (AUC) analysis suggested that combination of diagnostic proteins and CA125 achieved a much higher diagnostic accuracy compared with CA125 alone (AUC values: 0.98 versus 0.80), especially improved the specificity (0.97 versus 0.77). In addition, elevated plasma CRP levels were associated with increased risk of ovarian cancer. Conclusions Current study found that plasma protein CRP was an indicator for monitoring the progression of ovarian cancer. Combination of plasma protein biomarkers with CA125 could be utilized to early diagnose of ovarian cancer patients. Keywords ovarian cancer, proteomics, diagnosis, progression, CRP

Download Full-text