Advantages
- They can be detected with a small serum sample and is a good predictor of carcinogenesis within 5 years.
- Combined with existing indices and markers, it is possible to narrow down patients at higher risk of carcinogenesis.
Technology Overview & Background
Hepatocellular carcinoma is a malignant tumor that kills a large number of people worldwide, and many of these patients have chronic liver disease. Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common chronic liver disease, affecting approximately one in four people in Japan. Despite the large number of affected patients, the annual liver cancer rate from MASLD is less than 0.1%, and it is undesirable from the viewpoint of compliance and cost-effectiveness to perform abdominal echocardiography and blood tests at a high frequency for all patients as a liver cancer surveillance. Although few MASLD patients with a FIB4-index of less than 1.3 actually develop liver cancer, the FIB4-index alone is not effective in narrowing down the group at high risk of hepatocarcinogenesis, and biomarkers that can serve as further narrowing indicators were sought.
Therefore, they searched for biomarkers that correlate with hepatocarcinogenesis in MASLD patients and found Fibulin3 and GPNMB in serum. Fibulin3, GPNMB, and their mRNAs were significantly increased in MASLD patients with advanced liver fibrosis, and patients with high levels of these biomarkers had a very high carcinogenic rate. Combining these biomarkers with existing markers and indices such as AFP and FIB4-index is expected to make it possible to screen patients who need more detailed examination.
Data
- Proteomic analysis using serum exosomes from 50 MASLD patients showed that Fibulin3 was significantly increased in patients with advanced liver fibrosis.
- Serum Fibulin3 was measured by Circulex Human Fibulin-3/EFEMP1 ELISA and serum GPNMB level was measured by Human Osteoactivin/GPNMB DuoSet ELISA using stored serum from liver biopsies of 467 MASLD patients and confirmed the association of each with hepatocarcinogenesis.
- ROC curves for the development of hepatocarcinogenesis within 5 years were generated using serum Fibulin3 or GPNMB levels of MASLD patients, and AUROC was calculated from the threshold values calculated using Youden index. As a result, it was confirmed that any of the biomarkers could predict carcinogenesis within 3 years.
Publication(s)
Sakane S., Hikita H. et al. Hepatol. Commun. (2024) 8(6):e0448.
DOI: 10.1097/HC9.0000000000000448
Patent(s)
PCT/JP2023/022224 (preliminary stage of transition to designated country)
Principal Investigator & Academic Institution
Hayato HIKITA, MD, PhD (Lecturer, Graduate School of Medicine, Osaka University)
Expectations
TECH MANAGE is now looking for diagnostic companies that are interested in developing and commercializing diagnostic products for assessing the risk of developing liver cancer based on this invention. We also welcome in-house use of this invention by pharmaceutical companies, as it may be effective in recruiting subjects for the development of drugs for the prevention of MASLD carcinogenesis.
We can also arrange a direct meeting with the principal investigator on this topic. In addition, we can provide unpublished data and know-how through the conclusion of a CDA with Osaka University. We can also set up options such as exclusive evaluation before licensing the invention, so please feel free to contact us.
Project.JT-05028