HE4 protein and SMRP: Potential novel biomarkers in ovarian cancer detection

Fritz-Rdzanek, Anna; Grzybowski, Wojciech; Beta, J.; Durczyński, Andrzej; Jakimiuk, Artur

doi:10.3892/ol.2012.757

Cited by 15 publications

(15 citation statements)

References 42 publications

(57 reference statements)

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“…Mesothelin is over-expressed in EOC, involved in tumour progression (22, 23) and associated with chemoresistance and a poorer overall prognosis (24). It has also been proposed as a potential biomarker for EOC identification (25, 26), and in mesothelioma as a putative biomarker to monitor response to treatment (27). Our association between baseline mesothelin and risk of EOC progression may relate to increased disease burden.…”

Section: Discussionmentioning

confidence: 99%

Predicting Response to Bevacizumab in Ovarian Cancer: A Panel of Potential Biomarkers Informing Treatment Selection

Collinson

Hutchinson

Craven

et al. 2013

Clinical Cancer Research

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Purpose: The aim of this study was to identify and validate novel predictive and/or prognostic serum proteomic biomarkers in patients with epithelial ovarian cancer (EOC) treated as part of the phase III international ICON7 clinical trial.Experimental Design: ICON7 was a phase III international trial in EOC which showed a modest but statistically significant benefit in progression-free survival (PFS) with the addition of bevacizumab to standard chemotherapy. Serum samples from 10 patients who received bevacizumab (five responders and five nonresponders) were analyzed by mass spectrometry to identify candidate biomarkers. Initial validation and exploration by immunoassay was undertaken in an independent cohort of 92 patients, followed by a second independent cohort of 115 patients (taken from across both arms of the trial).Results: Three candidate biomarkers were identified: mesothelin, fms-like tyrosine kinase-4 (FLT4), and a 1 -acid glycoprotein (AGP). Each showed evidence of independent prognostic potential when adjusting for high-risk status in initial (P < 0.02) and combined (P < 0.01) validation cohorts. In cohort I, individual biomarkers were not predictive of bevacizumab benefit; however, when combined with CA-125, a signature was developed that was predictive of bevacizumab response and discriminated benefit attributable to bevacizumab better than clinical characteristics. The signature showed weaker evidence of predictive ability in validation cohort II, but was still strongly predictive considering all samples (P ¼ 0.001), with an improvement in median PFS of 5.5 months in signature-positive patients in the experimental arm compared with standard arm.Conclusions: This study shows a discriminatory signature comprising mesothelin, FLT4, AGP, and CA-125 as potentially identifying those patients with EOC more likely to benefit from bevacizumab. These results require validation in further patient cohorts.

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Section: Discussionmentioning

confidence: 99%

Predicting Response to Bevacizumab in Ovarian Cancer: A Panel of Potential Biomarkers Informing Treatment Selection

Collinson

Hutchinson

Craven

et al. 2013

Clinical Cancer Research

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“…It is highly expressed in mesothelioma, ovarian and pancreatic cancers and lung adenocarcinoma [7,23,24,27-29], but only expressed normally in mesothelial cells of the peritoneum, pericardium and pleura [27]. Like HE4, it has shown promise in the detection of early stage ovarian cancer, especially in combination with CA125 [1,30,31]. Improvements may be gained adding MSLN to a biomarker panel with CA125 and HE4 to detect early stage disease [15,31] although contradictory results have been reported [32,33].…”

Section: Introductionmentioning

confidence: 99%

“…Like HE4, it has shown promise in the detection of early stage ovarian cancer, especially in combination with CA125 [1,30,31]. Improvements may be gained adding MSLN to a biomarker panel with CA125 and HE4 to detect early stage disease [15,31] although contradictory results have been reported [32,33]. Levels of detection of MSLN from serum and plasma for ovarian cancer were shown to be similar [34].…”

Section: Introductionmentioning

confidence: 99%

“…Panels of biomarkers, able to cover the molecular heterogeneity of ovarian cancer [31,38], or specific to high grade serous carcinoma [12], will be the most effective way to detect early disease for fewer fatalities. To date, no panel has been identified that can achieve the sensitivity (>75%) and specificity (>99.6%) needed to meet the accepted criteria of no more than ten surgeries for every case of early stage ovarian cancer identified.…”

Section: Introductionmentioning

confidence: 99%

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Serum folate receptor alpha, mesothelin and megakaryocyte potentiating factor in ovarian cancer: association to disease stage and grade and comparison to CA125 and HE4

et al. 2013

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BackgroundEvaluate and compare the utility of serum folate receptor alpha (FRA) and megakaryocyte potentiating factor (MPF) determinations relative to serum CA125, mesothelin (MSLN) and HE4 for the diagnosis of epithelial ovarian cancer (EOC).MethodsElectrochemiluminescent assays were developed for FRA, MSLN and MPF and used to assess the levels of these biomarkers in 258 serum samples from ovarian cancer patients. Commercial assays for CA125 and HE4 were run on a subset of 176 of these samples representing the serous histology. Data was analyzed by histotype, stage and grade of disease. A comparison of the levels of the FRA, MSLN and MPF biomarkers in serum, plasma and urine was also performed in a subset of 57 patients.ResultsSerum and plasma levels of FRA, MSLN and MPF were shown to be highly correlated between the two matrices. Correlations between all pairs of markers in 318 serum samples were calculated and demonstrated the highest correlation between HE4 and MPF, and the lowest between FRA and MPF. Serum levels of all markers showed a dependence on both stage and grade of disease. A multi-marker logistic regression model was developed resulting in an AUC=0.91 for diagnosis of serous ovarian cancer, a significant improvement over the AUC for any of the individual markers, including CA125 (AUC=0.84).ConclusionsFRA has significant potential as a biomarker for ovarian cancer, both as a stand-alone marker and in combination with other known markers for EOC. The lack of correlation between the various markers analyzed in the present study suggests that a panel of markers can aid in the detection and/or monitoring of this disease.

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“…HE4 is commonly overexpressed in patients with serous endometriosis as well as epithelial ovarian and uterine cancer, and it is elevated in the serum of patients with ovarian cancer [12,13]. The main advantages in using HE4 for ovarian cancer detection reside in its high specificity for malignancy compared to the benign form of the disease [15] as well as in the fact that it is not only expressed in the disease's early stages but also serves as an early indicator of disease recurrence [12,13]. Therefore, HE4 is today of particular interest for recognizing early stages of epithelial ovarian cancer [15].…”

Section: Introductionmentioning

confidence: 98%

Alkaline phosphatase labeled antibody-based electrochemical biosensor for sensitive HE4 tumor marker detection

Čadková

Dvořáková

Metelka

et al. 2015

Electrochemistry Communications

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HE4 protein and SMRP: Potential novel biomarkers in ovarian cancer detection

Cited by 15 publications

References 42 publications

Predicting Response to Bevacizumab in Ovarian Cancer: A Panel of Potential Biomarkers Informing Treatment Selection

Predicting Response to Bevacizumab in Ovarian Cancer: A Panel of Potential Biomarkers Informing Treatment Selection

Serum folate receptor alpha, mesothelin and megakaryocyte potentiating factor in ovarian cancer: association to disease stage and grade and comparison to CA125 and HE4

Alkaline phosphatase labeled antibody-based electrochemical biosensor for sensitive HE4 tumor marker detection

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