Microarray Glycoprofiling of CA125 Improves Differential Diagnosis of Ovarian Cancer

Kowa Chen; Aleksandra Gentry-Maharaj; Matthew Burnell; Catharina Steentoft; Lara Patricia Marcos da Silva; Ulla Mandel; Ian Jacobs; Anne Dawnay; Usha Menon; Klas Ola Blixt

doi:10.1021/pr3010474

Microarray Glycoprofiling of CA125 Improves Differential Diagnosis of Ovarian Cancer

Kowa Chen, Aleksandra Gentry-Maharaj, Matthew Burnell, Catharina Steentoft, Lara Patricia Marcos da Silva, Ulla Mandel, Ian Jacobs, Anne Dawnay, Usha Menon, Klas Ola Blixt

67 Citationer (Scopus)

Abstract

The CA125 biomarker assay plays an important role in the diagnosis and management of primary invasive epithelial ovarian/tubal cancer (iEOC). However, a fundamental problem with CA125 is that it is not cancer-specific and may be elevated in benign gynecological conditions such as benign ovarian neoplasms and endometriosis. Aberrant O-glycosylation is an inherent and specific property of cancer cells and could potentially aid in differentiating cancer from these benign conditions, thereby improving specificity of the assay. We report on the development of a novel microarray-based platform for profiling specific aberrant glycoforms, such as Neu5Acα2,6GalNAc (STn) and GalNAc (Tn), present on CA125 (MUC16) and CA15-3 (MUC1). In a blinded cohort study of patients with an elevated CA125 levels (30-500 kU/L) and a pelvic mass from the UK Ovarian Cancer Population Study (UKOPS), we measured STn-CA125, ST-CA125 and STn-CA15-3. The combined glycoform profile was able to distinguish benign ovarian neoplasms from invasive epithelial ovarian/tubule cancer (iEOCs) with a specificity of 61.1% at 90% sensitivity. The findings suggest that microarray glycoprofiling could improve differential diagnosis and significantly reduce the number of patients elected for further testing. The approach warrants further investigation in other cancers.

Originalsprog	Engelsk
Tidsskrift	Journal of Proteome Research
Vol/bind	12
Udgave nummer	3
Sider (fra-til)	1408-18
Antal sider	11
ISSN	1535-3893
DOI	https://doi.org/10.1021/pr3010474
Status	Udgivet - 1 mar. 2013

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10.1021/pr3010474

http://pubs.acs.org/doi/abs/10.1021/pr3010474

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title = "Microarray Glycoprofiling of CA125 Improves Differential Diagnosis of Ovarian Cancer",

abstract = "The CA125 biomarker assay plays an important role in the diagnosis and management of primary invasive epithelial ovarian/tubal cancer (iEOC). However, a fundamental problem with CA125 is that it is not cancer-specific and may be elevated in benign gynecological conditions such as benign ovarian neoplasms and endometriosis. Aberrant O-glycosylation is an inherent and specific property of cancer cells and could potentially aid in differentiating cancer from these benign conditions, thereby improving specificity of the assay. We report on the development of a novel microarray-based platform for profiling specific aberrant glycoforms, such as Neu5Acα2,6GalNAc (STn) and GalNAc (Tn), present on CA125 (MUC16) and CA15-3 (MUC1). In a blinded cohort study of patients with an elevated CA125 levels (30-500 kU/L) and a pelvic mass from the UK Ovarian Cancer Population Study (UKOPS), we measured STn-CA125, ST-CA125 and STn-CA15-3. The combined glycoform profile was able to distinguish benign ovarian neoplasms from invasive epithelial ovarian/tubule cancer (iEOCs) with a specificity of 61.1% at 90% sensitivity. The findings suggest that microarray glycoprofiling could improve differential diagnosis and significantly reduce the number of patients elected for further testing. The approach warrants further investigation in other cancers.",

author = "Kowa Chen and Aleksandra Gentry-Maharaj and Matthew Burnell and Catharina Steentoft and {da Silva}, {Lara Patricia Marcos} and Ulla Mandel and Ian Jacobs and Anne Dawnay and Usha Menon and Blixt, {Klas Ola}",

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T1 - Microarray Glycoprofiling of CA125 Improves Differential Diagnosis of Ovarian Cancer

AU - Chen, Kowa

AU - Gentry-Maharaj, Aleksandra

AU - Burnell, Matthew

AU - Steentoft, Catharina

AU - da Silva, Lara Patricia Marcos

AU - Mandel, Ulla

AU - Jacobs, Ian

AU - Dawnay, Anne

AU - Menon, Usha

AU - Blixt, Klas Ola

PY - 2013/3/1

Y1 - 2013/3/1

N2 - The CA125 biomarker assay plays an important role in the diagnosis and management of primary invasive epithelial ovarian/tubal cancer (iEOC). However, a fundamental problem with CA125 is that it is not cancer-specific and may be elevated in benign gynecological conditions such as benign ovarian neoplasms and endometriosis. Aberrant O-glycosylation is an inherent and specific property of cancer cells and could potentially aid in differentiating cancer from these benign conditions, thereby improving specificity of the assay. We report on the development of a novel microarray-based platform for profiling specific aberrant glycoforms, such as Neu5Acα2,6GalNAc (STn) and GalNAc (Tn), present on CA125 (MUC16) and CA15-3 (MUC1). In a blinded cohort study of patients with an elevated CA125 levels (30-500 kU/L) and a pelvic mass from the UK Ovarian Cancer Population Study (UKOPS), we measured STn-CA125, ST-CA125 and STn-CA15-3. The combined glycoform profile was able to distinguish benign ovarian neoplasms from invasive epithelial ovarian/tubule cancer (iEOCs) with a specificity of 61.1% at 90% sensitivity. The findings suggest that microarray glycoprofiling could improve differential diagnosis and significantly reduce the number of patients elected for further testing. The approach warrants further investigation in other cancers.

AB - The CA125 biomarker assay plays an important role in the diagnosis and management of primary invasive epithelial ovarian/tubal cancer (iEOC). However, a fundamental problem with CA125 is that it is not cancer-specific and may be elevated in benign gynecological conditions such as benign ovarian neoplasms and endometriosis. Aberrant O-glycosylation is an inherent and specific property of cancer cells and could potentially aid in differentiating cancer from these benign conditions, thereby improving specificity of the assay. We report on the development of a novel microarray-based platform for profiling specific aberrant glycoforms, such as Neu5Acα2,6GalNAc (STn) and GalNAc (Tn), present on CA125 (MUC16) and CA15-3 (MUC1). In a blinded cohort study of patients with an elevated CA125 levels (30-500 kU/L) and a pelvic mass from the UK Ovarian Cancer Population Study (UKOPS), we measured STn-CA125, ST-CA125 and STn-CA15-3. The combined glycoform profile was able to distinguish benign ovarian neoplasms from invasive epithelial ovarian/tubule cancer (iEOCs) with a specificity of 61.1% at 90% sensitivity. The findings suggest that microarray glycoprofiling could improve differential diagnosis and significantly reduce the number of patients elected for further testing. The approach warrants further investigation in other cancers.

U2 - 10.1021/pr3010474

DO - 10.1021/pr3010474

M3 - Journal article

C2 - 23360124

SN - 1535-3893

VL - 12

SP - 1408

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JO - Journal of Proteome Research

JF - Journal of Proteome Research

IS - 3

ER -

Microarray Glycoprofiling of CA125 Improves Differential Diagnosis of Ovarian Cancer

Abstract

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