Screening for ovarian cancer: a pilot randomised controlled trial

Jacobs, Ian; Skates, Steven J.; MacDonald, Nicola; Menon, Usha; Rosenthal, Adam N.; Davies, Anthony; Woolas, Robert; Jeyarajah, Arjun; Sibley, Karen; Lowe, David; Oram, David

doi:10.1016/s0140-6736(98)10261-1

Cited by 516 publications

(224 citation statements)

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“…The joint detection of HE4 and CA125 can improve the diagnostic rate of ovarian cancer [14]. Hellström et al [15 ]and Jacobs et al [16 ]found that CA125 is the best molecular marker for the early diagnosis of ovarian cancer; however, new research has noted that HE4 has greater significance than CA125 in the early diagnosis of ovarian cancer [17]. Based on the principles of a control study, our experimental results confirmed that HE4 and CA125 expression in patients with ovarian tumors differed from that in healthy women.…”

Section: Discussionmentioning

confidence: 99%

CA125 and HE4: Measurement Tools for Ovarian Cancer

Zhao

2016

Gynecol Obstet Invest

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Aims: This study aimed to examine the clinical significance of carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4) serum levels in combination for ovarian cancer detection in patients. Methods: In total, 75 patients with ovarian cancer, 86 patients with benign ovarian tumors, 75 patients with endometriosis and 34 healthy women (as a control group) were selected from January 2012 to July 2015 at Anhui province hospitals. The sensitivity and specificity of detection of CA125, HE4 and combined CA125 + HE4 in serum were analyzed for each group. Results: HE4 and CA125 serum levels in the ovarian cancer group were higher than those in the other 3 groups (p < 0.001). The sensitivity of CA125 was higher than that of HE4 (88.2 vs. 54.7%, respectively), whereas the specificity of HE4 was higher than that of CA125 (97.9 vs. 67.4%, respectively). In contrast, the sensitivity and specificity of HE4 combined with CA125 were 82.7 and 91.4%, respectively. The receiver operating characteristic-area under the curve values of HE4, CA125 and HE4 + CA125 were 0.889, 0.893 and 0.925, respectively. Conclusions: Combined detection of CA125 with HE4 can improve the sensitivity and specificity of ovarian cancer diagnosis and has certain clinical significance that can guide treatment planning.

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Section: Discussionmentioning

confidence: 99%

CA125 and HE4: Measurement Tools for Ovarian Cancer

Zhao

2016

Gynecol Obstet Invest

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“…The most widely researched ovarian cancer marker is CA125, and in pilot screening studies the marker has shown some value in postmenopausal women; sensitivity of this marker for early stage, pre-clinical disease detection however remains unclear [6]. A number of tumor markers for ovarian cancer, alone or as a panel, have also been identified and evaluated recently [25][26][27][28], but a useful screening marker or panel of markers has not been clearly established.…”

Section: Discussionmentioning

confidence: 99%

“…But ultrasound outperforms blood testing with respect to sensitivity for early stage disease (although a direct randomized comparison has not yet been carried out) [4,5]. Trials of the antigen CA125 (MUC16) blood test, followed by ultrasound when CA125 values are elevated, have resulted in a PPV in excess of 20%, with a pre-clinical sensitivity of more than 70% [6,7]. Although in a large proportion of cases this strategy detected disease prior to the appearance of clinical symptoms, sensitivity for early stage disease using CA125>30U/ml was only about 40% [6].…”

Section: Introductionmentioning

confidence: 99%

“…Trials of the antigen CA125 (MUC16) blood test, followed by ultrasound when CA125 values are elevated, have resulted in a PPV in excess of 20%, with a pre-clinical sensitivity of more than 70% [6,7]. Although in a large proportion of cases this strategy detected disease prior to the appearance of clinical symptoms, sensitivity for early stage disease using CA125>30U/ml was only about 40% [6]. The combined CA125 and HE4 has only minimal increase in sensitivity and there is only a marginally significant mortality reduction as shown in the most recent UKCTOCS study [8].…”

Section: Introductionmentioning

confidence: 99%

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Use of Blood-based mRNA profiling to Identify Biomarkers for Ovarian Cancer Screening

Mok¹,

Kim²,

Skates³

et al. 2017

Gynecol Obstet

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Citation: Mok CS, Kim JH, Skates SJ, Schorge JO, Cramer DW, et al. (2017) AbstractPurpose: To identify candidate genomic signatures for the early detection of ovarian cancer using whole bloodbased gene expression profiles.Experimental Design: We performed Affymetrix U133Plus 2.0 GeneChip microarray analyses on whole blood RNA samples obtained from 14 ovarian cancer patients and 15 age-matched, healthy women. Genes differentially expressed were identified using a parametric Welch t-test. Real-time qRT-PCR analyses were performed on RNA prepared from 96 ovarian cancer patients and 83 age-matched healthy women, using primer sets specific for 14 genes. A Mann Whitney U test assessed individual gene significance. CA125 levels were determined in the same set of samples. We used logistic regression analyses and cross validation to assess the ability of linear combinations of specific transcripts combined with CA125 to distinguish cancer from controls. Results:Microarray analyses showed that 9583 probes were significantly different in blood gene expression profiles from healthy women as compared with those from ovarian cancer patients (p<0.05). Real-time RT-PCR analyses on the 96 cases and 83 controls validated 7 genes, which showed significantly different expression levels in cases and controls. Logistic regression analyses and cross validation identified an optimal panel of markers including CA125, BRCA1, and KIAA0562, that could improve the sensitivity of CA125 alone to over 90% at 98% specificity in the detection of early stage ovarian cancer. Conclusion:Circulating blood gene expression profiles identified RNA markers that can improve the sensitivity of CA125 in the detection of early stage ovarian cancer. Further validation is warranted to confirm the clinical usefulness of these biomarkers. Page 2 of 7Citation: Mok CS, Kim JH, Skates SJ, Schorge JO, Cramer DW, et al. (2017) Use of Blood-based mRNA profiling to Identify Biomarkers for Ovarian Cancer Screening. Gynecol Obstet (Sunnyvale) 7: 443.

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“…They should have several properties including: (i) sensitivity, selectivity, and a strong association with the disease; (ii) they should be measurable via noninvasive procedure; (iii) should be useful in the majority of the population; and (iv) have strong diagnostic, prognostic, and predictive significance [91]. Although it has been reported that a specific biomarker should have a positive predictive value of 100%, a specificity of 99.6%, and a sensitivity of 100% [92], it has not been easy finding a biomarker with a positive predictive value of 100% in all cases. It may also not be possible for all biomarkers to attain this level of accuracy because there will always be some variability and idiopathic differences, resulting in prediction error in real-life situations.…”

Section: Clinical Proteomicsmentioning

confidence: 99%

Proteomics in human cancer research

Pastwa

Somiari

Czyż

et al. 2007

Proteomics Clinical Apps

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Proteomics is now widely employed in the study of cancer. Many laboratories are applying the rapidly emerging technologies to elucidate the underlying mechanisms associated with cancer development, progression, and severity in addition to developing drugs and identifying patients who will benefit most from molecular targeted compounds. Various proteomic approaches are now available for protein separation and identification, and for characterization of the function and structure of candidate proteins. In spite of significant challenges that still exist, proteomics has rapidly expanded to include the discovery of novel biomarkers for early detection, diagnosis and prognostication (clinical application), and for the identification of novel drug targets (pharmaceutical application). To achieve these goals, several innovative technologies including 2-D-difference gel electrophoresis, SELDI, multidimensional protein identification technology, isotope-coded affinity tag, solid-state and suspension protein array technologies, X-ray crystallography, NMR spectroscopy, and computational methods such as comparative and de novo structure prediction and molecular dynamics simulation have evolved, and are being used in different combinations. This review provides an overview of the field of proteomics and discusses the key proteomic technologies available to researchers. It also describes some of the important challenges and highlights the current pharmaceutical and clinical applications of proteomics in human cancer research.

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Screening for ovarian cancer: a pilot randomised controlled trial

Cited by 516 publications

References 22 publications

CA125 and HE4: Measurement Tools for Ovarian Cancer

CA125 and HE4: Measurement Tools for Ovarian Cancer

Use of Blood-based mRNA profiling to Identify Biomarkers for Ovarian Cancer Screening

Proteomics in human cancer research

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