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

Kanoko Katoh & Kei Kawana et al.

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.

Authors
Kanoko Katoh, Yuki Katoh, Akiko Kubo, Miho Iida, Yuji Ikeda, Takashi Iwata, Hiroshi Nishio, Masaki Sugawara, Daiki Kato, Makoto Suematsu, Shuichi Hirai, Kei Kawana
Funding

Ministry of Education, Culture, Sports, Science and Technology

21K15602

Takeda Science Foundation

2021

The Seiichi Imai Memorial Foundation

2020

The Japan Society of Gynecologic Oncology

2022

Nihon University

Research Grant-in-aid for Early-Career Scientists 2020

MEXT | JST | Moonshot Research and Development Program

JP22zf0127007

MEXT | JST | Exploratory Research for Advanced Technology

Suematsu Gas Biology Project

Human Biology Microbiome Quantum Research Center