scholarly journals Proteomics Analysis for Finding Serum Markers of Ovarian Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yushan Cheng ◽  
Chongdong Liu ◽  
Nawei Zhang ◽  
Shengdian Wang ◽  
Zhenyu Zhang

A combination of peptide ligand library beads (PLLB) and 1D gel liquid chromatography-mass spectrometry/mass spectrometry (1DGel-LC-MS/MS) was employed to analyze serum samples from patients with ovarian cancer and from healthy controls. Proteomic analysis identified 1200 serum proteins, among which 57 proteins were upregulated and 10 were downregulated in the sera from cancer patients. Retinol binding protein 4 (RBP4) is highly upregulated in the ovarian cancer serum samples. ELISA was employed to measure plasma concentrations of RBP4 in 80 samples from ovarian cancer patients, healthy individuals, myoma patients, and patients with benign ovarian tumor, respectively. The plasma concentrations of RBP4 ranging from 76.91 to 120.08 ng/mL with the mean value89.13±1.67 ng/mL in ovarian cancer patients are significantly higher than those in healthy individuals (10.85±2.38 ng/mL). Results were further confirmed with immunohistochemistry, demonstrating that RBP4 expression levels in normal ovarian tissue were lower than those in ovarian cancer tissues. Our results suggested that RBP4 is a potential biomarker for diagnostic of screening ovarian cancer.

2021 ◽  
Vol 22 (12) ◽  
pp. 6501
Author(s):  
Violeta Morcuende-Ventura ◽  
Sonia Hermoso-Durán ◽  
Natalia Abian-Franco ◽  
Roberto Pazo-Cid ◽  
Jorge L. Ojeda ◽  
...  

(1) Background: Biophysical techniques applied to serum samples characterization could promote the development of new diagnostic tools. Fluorescence spectroscopy has been previously applied to biological samples from cancer patients and differences from healthy individuals were observed. Dendronized hyperbranched polymers (DHP) based on bis(hydroxymethyl)propionic acid (bis-MPA) were developed in our group and their potential biomedical applications explored. (2) Methods: A total of 94 serum samples from diagnosed cancer patients and healthy individuals were studied (20 pancreatic ductal adenocarcinoma, 25 blood donor, 24 ovarian cancer, and 25 benign ovarian cyst samples). (3) Results: Fluorescence spectra of serum samples (fluorescence liquid biopsy, FLB) in the presence and the absence of DHP-bMPA were recorded and two parameters from the signal curves obtained. A secondary parameter, the fluorescence spectrum score (FSscore), was calculated, and the diagnostic model assessed. For pancreatic ductal adenocarcinoma (PDAC) and ovarian cancer, the classification performance was improved when including DHP-bMPA, achieving high values of statistical sensitivity and specificity (over 85% for both pathologies). (4) Conclusions: We have applied FLB as a quick, simple, and minimally invasive promising technique in cancer diagnosis. The classification performance of the diagnostic method was further improved by using DHP-bMPA, which interacted differentially with serum samples from healthy and diseased subjects. These preliminary results set the basis for a larger study and move FLB closer to its clinical application, providing useful information for the oncologist during patient diagnosis.


2017 ◽  
Vol 114 (51) ◽  
pp. 13519-13524 ◽  
Author(s):  
Qing Wang ◽  
Ming Zhang ◽  
Tyler Tomita ◽  
Joshua T. Vogelstein ◽  
Shibin Zhou ◽  
...  

We here describe a selected reaction monitoring (SRM)-based approach for the discovery and validation of peptide biomarkers for cancer. The first stage of this approach is the direct identification of candidate peptides through comparison of proteolytic peptides derived from the plasma of cancer patients or healthy individuals. Several hundred candidate peptides were identified through this method, providing challenges for choosing and validating the small number of peptides that might prove diagnostically useful. To accomplish this validation, we used 2D chromatography coupled with SRM of candidate peptides. We applied this approach, called sequential analysis of fractionated eluates by SRM (SAFE-SRM), to plasma from cancer patients and discovered two peptides encoded by the peptidyl-prolyl cis–trans isomerase A (PPIA) gene whose abundance was increased in the plasma of ovarian cancer patients. At optimal thresholds, elevated levels of at least one of these two peptides was detected in 43 (68.3%) of 63 women with ovarian cancer but in none of 50 healthy controls. In addition to providing a potential biomarker for ovarian cancer, this approach is generally applicable to the discovery of peptides characteristic of various disease states.


2019 ◽  
Author(s):  
Wenjie Wang ◽  
Hongyu Xie ◽  
Bairong Xia ◽  
LiuChao Zhang ◽  
Ce Wang ◽  
...  

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


Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1309 ◽  
Author(s):  
Se Ik Kim ◽  
Nayeon Kang ◽  
Sangseob Leem ◽  
Jinho Yang ◽  
HyunA Jo ◽  
...  

We aimed to develop a diagnostic model identifying ovarian cancer (OC) from benign ovarian tumors using metagenomic data from serum microbe-derived extracellular vesicles (EVs). We obtained serum samples from 166 patients with pathologically confirmed OC and 76 patients with benign ovarian tumors. For model construction and validation, samples were randomly divided into training and test sets in the ratio 2:1. Isolation of microbial EVs from serum samples of the patients and 16S rDNA amplicon sequencing were carried out. Metagenomic and clinicopathologic data-based OC diagnostic models were constructed in the training set and then validated in the test set. There were significant differences in the metagenomic profiles between the OC and benign ovarian tumor groups; specifically, genus Acinetobacter was significantly more abundant in the OC group. More importantly, Acinetobacter was the only common genus identified by seven different statistical analysis methods. Among the various metagenomic and clinicopathologic data-based OC diagnostic models, the model consisting of age, serum CA-125 levels, and relative abundance of Acinetobacter showed the best diagnostic performance with the area under the receiver operating characteristic curve of 0.898 and 0.846 in the training and test sets, respectively. Thus, our findings establish a metagenomic analysis of serum microbe-derived EVs as a potential tool for the diagnosis of OC.


1998 ◽  
Vol 13 (3) ◽  
pp. 165-168 ◽  
Author(s):  
S. Krämer ◽  
M. Leeker ◽  
W. Jäger

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.


1993 ◽  
Vol 11 (8) ◽  
pp. 1506-1510 ◽  
Author(s):  
F J Xu ◽  
Y H Yu ◽  
L Daly ◽  
K DeSombre ◽  
L Anselmino ◽  
...  

PURPOSE At second-look surgical surveillance procedures, normal CA-125 levels can be associated with persistent disease in 50% to 60% of patients. A novel radioimmunoassay (RIA) has been evaluated for the ability to identify patients with persistent disease who have normal levels of CA-125. MATERIALS AND METHODS The OVX1 double-determinant assay used a murine monoclonal antibody to detect an epitope on a high-molecular weight mucin-like glycoprotein. RESULTS Apparently healthy individuals had serum OVX1 levels of 2.23 +/- 2.48 U/mL (mean +/- SD). Elevated serum OVX1 levels (> 7.2 U/mL) were found in 5% of 184 normal individuals and in 70% of 93 epithelial ovarian cancer patients with clinically evident disease. Among sera from these ovarian cancer patients, OVX1 was elevated in 68% of 76 samples with CA-125 levels more than 35 U/mL and in 76% of 17 samples with CA-125 levels less than 35 U/mL. In serum samples obtained at the time of positive second-look laparotomy, 59% of 41 patients with CA-125 levels less than 35 U/mL had elevated OVX1 antigen levels, whereas 41% of 22 patients with CA-125 levels more than 35 U/mL had elevated serum OVX1 levels. In patients with negative second-look laparotomies, false-positive results were eliminated by increasing the threshold of OVX1 to 10.5 U/mL. At this level, 32% of 41 patients with positive second-look operations had an elevated OVX1 level, despite a normal CA-125 level. When used in combination, CA-125 (> 35 U/mL) and OVX1 (> 10.5 U/mL) detected persistent disease in 56% of 63 patients with positive surveillance procedures, compared with 35% when CA-125 was used alone (P < .05). CONCLUSION An elevated OVX1 level can alert oncologists to the possibility that ovarian cancer has persisted, despite the return of CA-125 to a normal range.


Diagnostics ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 53
Author(s):  
Suchitra Kumari ◽  
A. Raj Kumar Patro ◽  
Baijayantimala Mishra ◽  
Saubhagya Kumar Jena ◽  
Sweta Singh

(1) Background: Lysyl oxidase (LOX) plays a dual role in carcinogenesis and studies show a higher risk of cancer in LOX G473A variants. The present study evaluated the pattern of LOX G473A polymorphism (rs1800449) and serum LOX levels in ovarian cancer patients. (2) Methods: Serum LOX levels were estimated by enzyme linked immunosorbent assay (ELISA). A polymorphism of rs1800449 of LOX gene was detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Selected samples were sequenced for external validation. (3) Results: A majority of study participants were from low socio-economic status. Serum LOX level was significantly higher in ovarian cancer patients as compared to control. Serum LOX level in early-stage ovarian cancer was significantly lower as compared to advanced stage (FIGO stage III & IV). Wild type GG genotype was used as reference. Genotypes AA were associated with a significant risk of epithelial ovarian cancer (OR 3.208; p value- 0.033). A allele of rs1800449 polymorphism of LOX gene, the odds ratio was 1.866 (95% Confidence Interval 1.112–3.16) p value = 0.017 (4) Conclusions: A allele of rs1800449 polymorphism of LOX gene presents an increased risk of ovarian cancer in East Indian population. Serum LOX levels could be a potential biomarker for the diagnosis and prognosis of ovarian cancer.


2022 ◽  
pp. 172460082110700
Author(s):  
Jia Chen ◽  
Dongting Yao ◽  
Weiqin Chen ◽  
Zhen Li ◽  
Yuanyuan Guo ◽  
...  

Objectives The aim of this study was to explore the diagnostic efficiency of serum exosomal miR-451a as a novel biomarker for pancreatic cancer. Methods Serum samples were collected prior to treatment. First, we analyzed microRNA (miRNA) profiles in serum exosomes from eight pancreatic cancer patients and eight healthy volunteers. We then validated the usefulness of the selected exosomal miRNAs as biomarkers in another 191 pancreatic cancer patients, 95 pancreatic benign disease (PB) patients, and 90 healthy controls. Results The expression of miR-451a in serum-derived exosomes from pancreatic cancer patients was significantly upregulated compared with those from PB patients and healthy individuals. Serum exosomal miR-451a showed excellent diagnostic power in identifying pancreatic cancer patients. In addition, exosomal miR-451a showed a significant association with clinical stage and distant metastasis in pancreatic cancer, and the expression level of serum exosomal miR-451a was sensitive to therapy and relapse. Conclusions Serum exosomal miR-451a might serve as a novel diagnostic marker for pancreatic cancer.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17033-e17033
Author(s):  
Pauline Wimberger ◽  
Simon Passek ◽  
Theresa Link ◽  
Yana Vassileva ◽  
Michael Kramer ◽  
...  

e17033 Background: Calretinin (CRT) is a calcium-binding protein, controlling intracellular calcium signaling. Besides its prominent expression in neurons, CRT has diagnostic implications in cancer, particularly in mesothelioma. In a recent liquid biopsy approach, plasma CRT level has been suggested for pre-diagnostic detection of mesothelioma. CRT is also expressed in serous ovarian cancer in about 23% of cases; however, clinical relevance of serum CRT is completely unknown and shall therefore be analyzed, herein. Methods: Serum calretinin (sCRT) was determined by calretinin enzyme-linked immunoabsorbent assay (DLD-Diagnostika GmbH, Hamburg) in a total of 380 serum samples from 134 ovarian cancer patients (thereof n = 115 (86%) with FIGO III or IV), including samples at primary diagnosis and at 4 follow-up reading points in the course of adjuvant treatment. Results: sCRT levels were significantly increased in ovarian cancer patients compared to healthy controls (ED = 0.3ng/ml, p < 0.001) and enabled an accurate discrimination between ovarian cancer and controls (AUC = 0.85). High sCRT levels at primary diagnosis predicted suboptimal debulking surgery without achieving macroscopically complete tumor resection (p < 0.001) and were associated with advanced FIGO-stage (p < 0.001) and high volume of ascites (p < 0.001). Increased sCRT levels at primary diagnosis were an independent predictor of poor PFS (HR:1.99, p = 0.018) and also indicated poor OS (HR:2.49, p = 0.008). Increased sCRT levels before and after platinum-based chemotherapy were independent predictors of poor OS (HR:15.4, p = 0.01; HR:5.59, p = 0.026). Moreover, elevated sCRT levels at primary diagnosis indicated platinum-resistance (p = 0.002). Conclusions: This is the first study, suggesting sCRT as an innovative liquid biopsy marker for ovarian cancer by showing its independent prognostic relevance and its association with primary platinum-resistance.


Sign in / Sign up

Export Citation Format

Share Document