SomaScan proteomics reveals novel biomarkers in the progression of liver cirrhosis to hepatocellular carcinoma.

BACKGROUND

Hepatocellular carcinoma (HCC) typically develops from liver cirrhosis (LC), however early diagnosis is difficult due to a lack of reliable biomarkers. The goal of this study was to use SomaScan proteomics technology to find plasma protein profiles that differentiated LC and HCC from healthy controls in order to develop novel biomarkers for HCC early detection and targeted therapy.

METHODS

We used SomaScan technology to evaluate 10,893 plasma proteins from LC, HCC, and normal populations. Differentially expressed proteins (DEPs) were discovered and functionally annotated using HPA, GO/KEGG, and PPI networks. Venn analysis was used to identify DEPs that were expressed in both LC and HCC.

RESULTS

There were 402 DEPs in LC and 389 in HCC, with MAPK signaling and neutrophil extracellular trap generation being the primary dysregulated pathways in LC and HCC, respectively. In addition, 38 co-expressed DEPs (e.g., SSX7, HIP1R, SLC25A18) were discovered in LC and HCC, including 9 previously unknown potential DEPs. PPI network analysis revealed that FLT4 and PDGFA were key drivers of LC progression to HCC. ELISA experiments confirmed that FLT4 and PDGFA are consistently down-regulated in the progression of LC to HCC (P < 0.05).

CONCLUSIONS

This investigation described the plasma proteomes of LC and HCC and identified FLT4 and PDGFA as possible early screening targets for HCC, establishing a scientific foundation for HCC detection in high-risk LC populations.