REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker

Laura Lehtinen; Pia Vesterkvist; Pia Roering; Taina Korpela; Liisa Hattara; Katja Kaipio; John-Patrick Mpindi; Johanna Hynninen; Annika Auranen; Ben Davidson; Caj Haglund; Kristiina Iljin; Seija Grenman; Harri Siitari; Olli Carpen

doi:10.1371/journal.pone.0151590

REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker

Laura Lehtinen (Corresponding Author), Pia Vesterkvist, Pia Roering, Taina Korpela, Liisa Hattara, Katja Kaipio, John-Patrick Mpindi, Johanna Hynninen, Annika Auranen, Ben Davidson, Caj Haglund, Kristiina Iljin, Seija Grenman, Harri Siitari, Olli Carpen

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Abstract

Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer.

Original language	English
Article number	e0151590
Journal	PLoS ONE
Volume	11
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0151590
Publication status	Published - 2016
MoE publication type	A1 Journal article-refereed

Keywords

ovarian cancer
biomarker
REG4

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0151590

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Lehtinen, L., Vesterkvist, P., Roering, P., Korpela, T., Hattara, L., Kaipio, K., Mpindi, J.-P., Hynninen, J., Auranen, A., Davidson, B., Haglund, C., Iljin, K., Grenman, S., Siitari, H., & Carpen, O. (2016). REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker. PLoS ONE, 11(3), Article e0151590. https://doi.org/10.1371/journal.pone.0151590

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abstract = "Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer.",

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AU - Lehtinen, Laura

AU - Vesterkvist, Pia

AU - Roering, Pia

AU - Korpela, Taina

AU - Hattara, Liisa

AU - Kaipio, Katja

AU - Mpindi, John-Patrick

AU - Hynninen, Johanna

AU - Auranen, Annika

AU - Davidson, Ben

AU - Haglund, Caj

AU - Iljin, Kristiina

AU - Grenman, Seija

AU - Siitari, Harri

AU - Carpen, Olli

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N2 - Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer.

AB - Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer.

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KW - biomarker

KW - REG4

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DO - 10.1371/journal.pone.0151590

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JF - PLoS ONE

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ER -

REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker

Abstract

Keywords

UN SDGs

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