A previously unidentified protein suggests a new way to diagnose ovarian cancer

A study led by the University of Nagoya in Japan has identified three previously unknown membrane proteins in ovarian cancer. Using a unique technology consisting of nanowires with a polyketone coating, the group succeeded in capturing the protein, demonstrating a new detection method for identifying ovarian cancer.

The discovery of new biomarkers is important for detecting ovarian cancer, because the disease is difficult to detect in its early stages when it is most easily treated. One approach to detecting cancer is to look for extracellular vesicles (EVs), especially small proteins released from tumors called exosomes. Because these proteins are found outside cancer cells, they can be isolated from body fluids, such as blood, urine, and saliva. However, the use of this biomarker is hindered by the lack of a reliable one to detect ovarian cancer.

A research group led by Akira Yokoi (he, she) of Nagoya University Graduate School of Medicine and Mayu Ukai (he, she) at the Institute for Advanced Research extracted small and medium/large EV from high-grade serous carcinoma (HGSC), a type of cancer the most common ovary, and analyze it using liquid chromatography-mass spectrometry to analyze protein.

Initially their research was challenging. “The validation step for identified proteins is very difficult because we have to try many antibodies before finding a good target,” said Yokoi. “As a result, it became clear that small and medium/large EVs are loaded with distinctly different molecules. Further investigation revealed that small EV is a more suitable biomarker than medium and large types. We identified membrane proteins FRα, Claudin-3, and TACSTD2 in HGSC-associated small EVs.”

Now that the group has identified the protein, they are investigating whether they can capture EVs in a way that allows identification of the presence of cancer. To do this, they turned to nanowire specialist Takao Yasui of the Graduate School of Engineering at Nagoya University who combined his research with that of Dr. Inokuma at the Japan Agency for Science and Technology to manufacture polyketone chain-coated nanowires (pNWs). This technology is ideal for separating exosomes from blood samples.

“The creation of pNWs is very difficult,” said Yokoi. “We had to try 3-4 different layers on the nanowires. Although polyketones are a completely new material to be used for coating these types of nanowires, in the end, they are a perfect match.”

“Our findings show that each of the three identified proteins is useful as a biomarker for HGSC,” said Yokoi. “The results of this study indicate that this diagnostic biomarker can be used as a predictive marker for certain therapies. Our results enable clinicians to optimize their therapeutic strategies for ovarian cancer, therefore, they may be useful for realizing personalized treatment.”