A Korean research team proposed a detailed classification method based on cancer stem cell RNA characteristics and customized, targeted therapy for intractable hepatocellular carcinoma (HCC) that does not respond to existing treatments.

The research team, led by professor Lee Sung-hwan at the Department of Surgery of CHA Bundang Medical Center, published the study in the latest issue of Cancer Communications.

The University of Texas MD Anderson Cancer Center in Houston, the U.S., jointly conducted the study.

Professor Lee’s team classified molecular subtypes with characteristics of cancer stem cells in intractable HCC.

The analysis showed that each molecular subtype had a different liver cancer progression.

Also, the team identified why each subtype had different therapy resistance.

The researchers divided HCC tumors into hepatic stem cell type 1 (HS1), hepatic stem cell type 2 (HS2), or differentiated HCC (dHCC) subtypes based on the similarity of RNA transcript expression patterns in HCC cells.

They found that each group had different molecular characteristics and evolutions of HCC.

The analysis of overall survival showed that survival rates in the HS1 and HS2 groups were lower than that of the dHCC group.

In particular, the dHCC group showed a 43.5 percent immunotherapy response, while the HS1 showed a low 17.6 percent immunotherapy response, and the HS2 group had 17.37 percent.

In joint research with Mayo Clinic, the researchers also developed a blood biomarker that can distinguish between two subtypes, HS1 and HS2, using serum samples of HCC patients.

“In this study, we could explain the fundamental cause of therapy resistance in refractory HCC patients at the molecular level with the characteristics of cancer stem cell-based RNA transcript,” Lee said.

He anticipated that classifying HCC patients more precisely and applying customized treatment could become a new option for the diagnosis and treatment of refractory HCC.