**Diagnosis and Screening**

[88] Goldstein G, Scheid MS, Hammerling V, Boyse EA, Schlesinger DH, Niall HD. Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells. Proceedings of the National Academy of Sciences USA.

[89] Goldknopf IL, Busch H. Isopeptide linkage between nonhistone and histone 2A polypeptides of chromosomal conjugate-protein A24. Proceedings of the National Academy

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1975;**72**:11-15

154 Ovarian Cancer - From Pathogenesis to Treatment

1980;**77**:1783-1786

of Sciences USA. 1977;**74**:864-868

**Chapter 7**

**Provisional chapter**

**The Role of Circulating Biomarkers in the Early**

**The Role of Circulating Biomarkers in the Early** 

DOI: 10.5772/intechopen.75484

Ovarian cancer is the leading cause of gynecologic-related cancer death and epithelial ovarian cancer (EOC) is the most lethal sub-type. EOC is usually asymptomatic, and few screening tests are available. Diagnosis of ovarian cancer can be difficult because of the nonspecific symptoms. Despite the various diagnostic methods used, there is no reliable early diagnostic test and it needs to be developed. Specific biomarkers may have potential with the least possible invasive procedure. Biomarkers with a high sensitivity to ovarian cancer should be identified. Circulating biomarkers that are significant tools for non-invasive early diagnosis can be analyzed using circulating tumor cells, exosomes, and circulating nucleic acids. Protein, gene, metabolite, and miRNA-based biomarkers can be used for ovarian cancer diagnosis. As non-coding RNAs, MiRNAs may have an important role in ovarian cancer diagnosis due to their effects on mRNA expression levels. The most recent developments regarding the potential of circulating biomarkers to

**Keywords:** ovarian cancer, biomarker, cell-free nucleic acids, early diagnosis, miRNA

Ovarian cancer is a heterogeneous disease and the most important cause of gynecological cancer-induced deaths [1]. It is the fifth most important cause of cancer-related deaths among women in the world [2]. Different types of tumors may develop from each cell type. These tumors are epithelial tumors, germ cell tumors (originating from the ovary cell and follicular),

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

**Diagnosis of Ovarian Cancer**

**Diagnosis of Ovarian Cancer**

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

detect early ovarian cancer is presented in this chapter.

Ece Gumusoglu and Tuba Gunel

Ece Gumusoglu and Tuba Gunel

http://dx.doi.org/10.5772/intechopen.75484

**Abstract**

**1. Introduction**

and stromal tumors [3].

#### **Chapter 7 Provisional chapter**

#### **The Role of Circulating Biomarkers in the Early Diagnosis of Ovarian Cancer The Role of Circulating Biomarkers in the Early Diagnosis of Ovarian Cancer**

DOI: 10.5772/intechopen.75484

Ece Gumusoglu and Tuba Gunel Ece Gumusoglu and Tuba Gunel

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.75484

#### **Abstract**

Ovarian cancer is the leading cause of gynecologic-related cancer death and epithelial ovarian cancer (EOC) is the most lethal sub-type. EOC is usually asymptomatic, and few screening tests are available. Diagnosis of ovarian cancer can be difficult because of the nonspecific symptoms. Despite the various diagnostic methods used, there is no reliable early diagnostic test and it needs to be developed. Specific biomarkers may have potential with the least possible invasive procedure. Biomarkers with a high sensitivity to ovarian cancer should be identified. Circulating biomarkers that are significant tools for non-invasive early diagnosis can be analyzed using circulating tumor cells, exosomes, and circulating nucleic acids. Protein, gene, metabolite, and miRNA-based biomarkers can be used for ovarian cancer diagnosis. As non-coding RNAs, MiRNAs may have an important role in ovarian cancer diagnosis due to their effects on mRNA expression levels. The most recent developments regarding the potential of circulating biomarkers to detect early ovarian cancer is presented in this chapter.

**Keywords:** ovarian cancer, biomarker, cell-free nucleic acids, early diagnosis, miRNA

#### **1. Introduction**

Ovarian cancer is a heterogeneous disease and the most important cause of gynecological cancer-induced deaths [1]. It is the fifth most important cause of cancer-related deaths among women in the world [2]. Different types of tumors may develop from each cell type. These tumors are epithelial tumors, germ cell tumors (originating from the ovary cell and follicular), and stromal tumors [3].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular and cellular analyses of these tumor types may lead to earlier diagnosis of ovarian cancer and it is hoped better survival rates. Many factors play a role in the development of cancer, while genomic mutations and epigenetic changes are very important. For this reason, studies on mutations and epigenetic alterations may provide information about features such as early diagnosis, surveillance, and response to treatment.

**Gene Gene full name Protein class Scorea No. of** 

1–3-N-acetylgalactosaminyltransferase and

ATAD5 ATPase family, AAA domain containing 5 Nucleic acid

BRCA2 BRCA2, DNA repair associated Nucleic acid

PGR Progesterone receptor Transcription factor;

EGF Epidermal growth factor Extracellular matrix

ESR1 Estrogen receptor 1 Transcription factor;

alpha 1–3-galactosyltransferase

ABO ABO, alpha

EHMT2 Euchromatic histone lysine methyltransferase 2

PIK3CA Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha

ERCC1 ERCC excision repair 1, endonuclease non-

catalytic subunit

TP53 Tumor protein p53 Transcription factor 0.245958 144 2 CLDN7 Claudin 7 Cell junction protein 0.201099 5 0

SYNPO2 Synaptopodin 2 Cytoskeletal protein 0.200275 1 0 GPX6 Glutathione peroxidase 6 Oxidoreductase 0.200275 1 0 RSPO1 R-spondin 1 0.200275 1 0 WNT4 Wnt family member 4 Signaling molecule 0.200275 1 0

MIR376C MicroRNA 376c 0.2 1 0 BRCA1 BRCA1, DNA repair associated 0.02933 99 5 ERBB2 erb-b2 receptor tyrosine kinase 2 0.017792 57 0

VEGFA Vascular endothelial growth factor A Signaling molecule 0.012847 39 0 MUC16 Mucin 16, cell-surface associated 0.009 25 0 EGFR Epidermal growth factor receptor 0.008176 22 0

IGF2 Insulin like growth factor 2 0.006253 15 1 NBR1 NBR1, autophagy cargo receptor 0.006044 22 0 CDKN1A Cyclin dependent kinase inhibitor 1A Enzyme modulator 0.005704 13 0 TNF Tumor necrosis factor Signaling molecule 0.005704 13 0 ABCB1 ATP binding cassette subfamily B member 1 0.005495 20 3

binding

binding

receptor; nucleic acid binding

protein; receptor

receptor; nucleic acid binding

Nucleic acid binding

Transferase; nucleic acid binding

**PMIDsb**

http://dx.doi.org/10.5772/intechopen.75484

0.200275 1 0

0.2 1 0

0.01422 44 4

0.007287 10 0

0.007077 18 0

0.006528 16 0

0.006528 16 0

Transferase; kinase 0.007627 20 3

Transferase 0.200549 3 0

The Role of Circulating Biomarkers in the Early Diagnosis of Ovarian Cancer

**No. of SNPsc**

159
