Diagnostic accuracy of urine HE4 in patients with ovarian cancer: a meta-analysis

Jia, Mengmeng; Deng, Jiehui; Cheng, Xiaolin; Zhen, Yan; Li, Qingchun; Xing, Yingying; Fan, Daiming; Tian, Xiaoyu

doi:10.18632/oncotarget.14173

Cited by 28 publications

(25 citation statements)

References 35 publications

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“…One of the serine protease inhibitor families predicted to function in the innate immune system in the lung is the evolutionarily conserved group of whey acidic protein (WAP) four-disulfide core (FDC) proteins (WFDC protein family; Bingle and Vyakarnam, 2008). The WFDC signature – eight conserved cysteine residues linked by four disulfide bonds – is often found in antimicrobial and antifungal molecules (Jia et al, 2017; Scaletta et al, 2017), and inhibits protease activity (Bingle and Vyakarnam, 2008). Among the 14 WFDC mammalian genes (at least), many map to a cluster on chromosome 20q12-13 in humans (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…This genomic region is amplified in many epithelial cancers, including breast, colon, lung, ovarian, pancreatic and stomach (Liu et al, 2013; O'Neal et al, 2013). In patients with serous and endometrioid epithelial ovarian carcinomas, a high serum WFDC2 level has been reported, and affords a good diagnostic and prognostic marker (Drapkin et al, 2005; Jia et al, 2017; Scaletta et al, 2017). Supporting the idea that the protein not only marks cancer cells but promotes cancerous growth, overexpression of WFDC2 reportedly induces the proliferation and invasion of human ovarian cancer cells (Moore et al, 2014; Zhu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Lack of whey acidic protein four disulphide core (WFDC) 2 protease inhibitor causes neonatal death from respiratory failure in mice

Nakajima

Ono

Radović

et al. 2019

Disease Models &Amp; Mechanisms

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Respiratory failure is a life-threatening problem for pre-term and term infants, yet many causes remain unknown. Here, we present evidence that whey acidic protein (WAP) four-disulfide core domain protease inhibitor 2 (Wfdc2), a protease inhibitor previously unrecognized in respiratory disease, may be a causal factor in infant respiratory failure. Wfdc2 transcripts are detected in the embryonic lung and analysis of a Wfdc2-GFP knock-in mouse line shows that both basal and club cells, and type II alveolar epithelial cells (AECIIs), express Wfdc2 neonatally. Wfdc2-null-mutant mice display progressive atelectasis after birth with a lethal phenotype. Mutant lungs have multiple defects, including impaired cilia and the absence of mature club cells from the tracheo-bronchial airways, and malformed lamellar bodies in AECIIs. RNA sequencing shows significant activation of a pro-inflammatory pathway, but with low-quantity infiltration of mononuclear cells in the lung. These data demonstrate that Wfdc2 function is vitally important for lung aeration at birth and that gene deficiency likely causes failure of the lung mucosal barrier.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lack of whey acidic protein four disulphide core (WFDC) 2 protease inhibitor causes neonatal death from respiratory failure in mice

Nakajima

Ono

Radović

et al. 2019

Disease Models &Amp; Mechanisms

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show abstract

“…Esta investigación fue realizada para evaluar la utilidad de HE4 en la detección precoz de cáncer ovárico de células epiteliales comparándolo frente a CA125 e índice ROMA, para los cuales se consideró puntos de corte preestablecidos en cada variable a evaluar. Diferentes estudios sugieren que HE4 es superior a CA125 para distinguir entre enfermedades ováricas malignas y benignas [22][23][24][25][26][27]. Los resultados muestran que HE4 presenta un valor medio altamente diferenciable, que permite distinguir entre mujeres con masas pélvicas malignas de las benignas (7.19 versus 5.71; control 5.79), al contrario de CA125 e I. ROMA (5.72 versus 4.64; control 4.57 y 5.92 versus 2.29; control 3.50, respectivamente).…”

Section: Discussionunclassified

Utilidad de la Proteína Epididimal Humana 4 (HE4) en la detección de Cáncer de ovario.

Nájera¹,

Morey-León

Salas

et al. 2018

Rev. Oncol. Ecu

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Introducción: El cáncer de ovario epitelial aunque tiene baja prevalencia está considerado entre las malignidades ginecológicas más letales por su alta mortalidad. El interés en la detección temprana del cáncer de ovario como mecanismo para lograr la reducción de la mortalidad ha crecido con el descubrimiento de biomarcadores tumorales séricos asociados a tumores malignos. El presente estudio plantea determinar la eficacia del uso del biomarcador HE4 para la detección precoz de cáncer epitelial de ovario en estadios tempranos. Métodos: Se evaluaron pacientes con masas pélvicas entre abril de 2015 y marzo de 2016. Valores de sensibilidad, especificidad, predictivo positivo y negativo, razón de probabilidad positiva y negativa, y pruebas estadísticas fueron calculados para determinar la relación entre los estados menopáusicos, y los grupos de acuerdo con el resultado histológico (benigno, maligno y control) de HE4, CA125 y ROMA. Resultados: Ingresaron al estudio 53 pacientes. La proteína epididimal humana 4 - HE4 presentó un valor medio diferenciable que permite distinguir masas pélvicas malignas (HE4:7,19 (maligno) vs. 5,71 (benigno)), igualmente la combinación HE4 + ROMA presentan mayor sensibilidad y especificidad (S: 100 %; E: 94.29 %) que las combinaciones CA125 + HE4 y CA125 + ROMA (S: 80 % y 88.89 %; E: 75.76 % y 77.14 %). Conclusión: Los resultados sugieren que HE4 serviría como un biomarcador eficiente para la diferenciación de masas pélvicas en estadios tempranos y si se adiciona el estatus menopaúsico, e índice ROMA afianzaría los resultados, permitiendo la diferenciación del cáncer de ovario epitelial en estadios tempranos en el país.

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“…The authors found the use of urinary HE4 to be sensitive and highly specific for the diagnosis of OC and suggested that diagnosis for OC using this non-invasive method could be highly efficient. 38,39 It was also demonstrated that HE4 can be detected in the urine of OC patients at a specificity level of 94.4%, including those with stage I/II disease. This data indicated that measuring HE4 in the urine may aid early-stage diagnosis and help to monitor the response of therapy leading to the effective generation of treatment plans for patients.…”

Section: Current Biomarkers For Ocmentioning

confidence: 95%

“…36,37 A systematic analysis was conducted to evaluate the diagnostic value for HE4 in detecting OC. 38 The quality of studies included in the analysis was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Seven publications were used in the analysis that encompassed 413 OC patients and 573 controls.…”

Section: Current Biomarkers For Ocmentioning

confidence: 99%

Urine Biomarkers for the Early Detection of Ovarian Cancer – Are We There Yet?

et al. 2019

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Ovarian cancer affects around 7500 women in the United Kingdom every year. Despite this, there is no effective screening strategy or standard treatment for ovarian cancer. If diagnosed during stage I, ovarian cancer has a 90% 5-year survival rate; however, there is usually a masking of symptoms which leads to an often late-stage diagnosis and correspondingly poor survival rate. Current diagnostic methods are invasive and consist of a pelvic examination, transvaginal ultrasonography, and blood tests to detect cancer antigen 125 (CA125). Unfortunately, surgery is often still required to make a positive diagnosis. To address the need for accurate, specific, and non-invasive diagnostic methods, there has been an increased interest in biomarkers identified through non-invasive tests as tools for the earlier diagnosis of ovarian cancer. Although most studies have focused on the identification of biomarkers in blood, the ease of availability of urine and the high patient compliance rates suggest that it could provide a promising resource for the screening of patients for ovarian cancer.

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Diagnostic accuracy of urine HE4 in patients with ovarian cancer: a meta-analysis

Cited by 28 publications

References 35 publications

Lack of whey acidic protein four disulphide core (WFDC) 2 protease inhibitor causes neonatal death from respiratory failure in mice

Lack of whey acidic protein four disulphide core (WFDC) 2 protease inhibitor causes neonatal death from respiratory failure in mice

Utilidad de la Proteína Epididimal Humana 4 (HE4) en la detección de Cáncer de ovario.

Urine Biomarkers for the Early Detection of Ovarian Cancer – Are We There Yet?

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