Serum Free Fatty Acid Changes Caused by High Expression of Stearoyl-CoA Desaturase 1 in Tumor Tissues Are Early Diagnostic Markers for Ovarian Cancer

Author:

Katoh Kanoko1ORCID,Katoh Yuki23ORCID,Kubo Akiko4ORCID,Iida Miho5ORCID,Ikeda Yuji1ORCID,Iwata Takashi3ORCID,Nishio Hiroshi3ORCID,Sugawara Masaki3ORCID,Kato Daiki6ORCID,Suematsu Makoto47ORCID,Hirai Shuichi2ORCID,Kawana Kei1ORCID

Affiliation:

1. 1Department of Obstetrics and Gynecology, Nihon University School of Medicine, Tokyo, Japan.

2. 2Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan.

3. 3Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.

4. 4Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan.

5. 5Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan.

6. 6Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

7. 7WPI-Bio2Q Research Center and Central Institute for Experimental Animals, Kawasaki, Japan.

Abstract

Ovarian cancer has a poor prognosis and is difficult to detect in early stages. Therefore, developing new diagnostic markers for early-stage ovarian cancer is critical. Here, we developed a diagnostic marker for early-stage ovarian cancer on the basis of fatty acid metabolism characteristics of cancer cells. The expression of various fatty acid metabolizing enzymes such as stearoyl-CoA desaturase 1 (SCD1) was altered in early-stage ovarian cancer tissue compared with that in normal ovarian tissue. Changes in the expression of fatty acid metabolizing enzymes, particularly SCD1, in cancer tissues were found to alter concentrations of multiple free fatty acids (FFA) in serum. We were the first to show that fatty acid metabolic characteristics in tissues are related to the FFA composition of serum. Surprisingly, patients with stage I/II ovarian cancer also showed significant changes in serum levels of eight FFAs, which can be early diagnostic markers. Finally, using statistical analysis, an optimal early diagnostic model combining oleic and arachidic acid levels, fatty acids associated with SCD1, was established and confirmed to have higher diagnostic power than CA125, regardless of histology. Thus, our newly developed diagnostic model using serum FFAs may be a powerful tool for the noninvasive early detection of ovarian cancer. Significance: Measurement of serum FFA levels by changes in the expression of fatty acid metabolizing enzymes in tumor tissue would allow early detection of ovarian cancer. In particular, the SCD1-associated FFAs, oleic and arachidic acid, would be powerful new screening tools for early-stage ovarian cancer.

Funder

Ministry of Education, Culture, Sports, Science and Technology

Takeda Science Foundation

The Seiichi Imai Memorial Foundation

The Japan Society of Gynecologic Oncology

Nihon University

MEXT | JST | Moonshot Research and Development Program

MEXT | JST | Exploratory Research for Advanced Technology

Human Biology Microbiome Quantum Research Center

Publisher

American Association for Cancer Research (AACR)

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