Recently, researchers from the CNHPP Alliance, the State Key Laboratory of Proteomics, Beijing University of Technology and Fudan University published an article entitled "Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma" in Nature.

The article, by comparing the analyses of proteomics and phosphoproteomics, identified proteomic features in early hepatocellular carcinoma (HCC), and provided a new target for early treatment of HCC.

HCC is a type of cancer with the third-ranked fatality rate across the globe. And in Southeast Asia, HCC is mainly caused by infection with hepatitis B virus (HBV). Although the therapeutic efficacy of early HCC is ideal, the overall five-year survival rate for patients with only HCC ranges from 50 percent to 70 percent.

Using proteomics and phosphoproteomics analysis, the researchers characterized 110 tumor and non-tumor tissues of clinically early-stage HCC associated with hepatitis B virus infection.

Quantitative proteomic analysis found that early HCC is heterogeneous and can be divided into three subtypes: S-I, S-II and S-III.

Among them, patients with S-III subtype had impaired cellular cholesterol homeostasis, and they showed the lowest overall survival rate after surgery and the greatest risk of poor prognosis.

In addition, the high expression of sterol O-acyltransferase 1 (SOAT1) is a characteristic of the S-III subtype. After knocking out the gene encoding the enzyme, the distribution of cellular cholesterol is changed, which can effectively inhibit the proliferation and migration of HCC.

The researchers constructed a patient-derived HCC tumor xenograft mouse model, which was significantly reduced in size after treating it with SOAT1 inhibitor avasimibe. (Excerpt from Nature, Published: 27 February 2019)