Clinical observation of the association between cancer aggressiveness and embryonic development stage implies the importance of developmental signals in cancer initiation and therapeutic resistance. However, the dynamic gene expression during organogenesis and the master oncofetal drivers are still unclear, which impeded the efficient elimination of poor prognostic tumors, including human hepatocellular carcinoma (HCC). In this study, human embryonic stem cells were induced to differentiate into adult hepatocytes along hepatic lineages to mimic liver development in vitro. Combining transcriptomic data from liver cancer patients with the hepatocyte differentiation model, the active genes derived from different hepatic developmental stages and the tumor tissues were selected. Bioinformatic analysis followed by experimental assays was used to validate the tumor subtype-specific oncofetal signatures and potential therapeutic values. Hierarchical clustering analysis revealed the existence of two subtypes of liver cancer with different oncofetal properties. The gene signatures and their clinical significance were further validated in an independent clinical cohort and The Cancer Genome Atlas database. Upstream activator analysis and functional screening further identified E2F1 and SMAD3 as master transcriptional regulators. Small-molecule inhibitors specifically targeting the oncofetal drivers extensively down-regulated subtype-specific developmental signaling and inhibited tumorigenicity. Liver cancer cells and primary HCC tumors with different oncofetal properties also showed selective vulnerability to their specific inhibitors. Further precise targeting of the tumor initiating steps and driving events according to subtype-specific biomarkers might eliminate tumor progression and provide novel therapeutic strategy.

AMC and RC are co-inventors on US Patent no. 9,198,911 filed by Columbia University and licensed to Aclaris Therapeutics. RC is a consultant for and shareholder of Aclaris Therapeutics. AMC is a consultant for Aclaris Therapeutics and Dermira and is a shareholder of Aclaris Therapeutics. AMC has received grant support from Pfizer.

The treatment technics for substrate was researched and improved by experimentations, the technics and additive research of plating for forming ornamental and functional multicomponents alloy was carried out completely, the optimum technics of plating multicomponents alloy was been found. The coatings made by optimum technics were with excellent corrosion-resistance ,wear-resistance, oxidation-resistance and with a smooth, fine, shining surface. It was proved that the 8.9% phosphorus in the coating and the coating was amorphous crystal by determinations. And it was found that the combination force between the substrate and the coating was vary good and the properties of coating to resist corrosion and abrasion were much better than that of Ni-P alloy through the tests.The coating was finery in ornamentally also.

The electroless plating technics of copper on plastic substrate was researched, and on this basis, the Ni-W-P alloy plating technics on aforementioned plastic substrate was researched. The optimum electroless plating technics, plating technics and bath were found. The coating made in optimum technics was excellent in corrosion-resistance, wear-resistance, oxidation-resistance, and with a smooth, fine, shining surface. It was proved that the 8.1% phosphorus in the coating and the coating was amorphous crystal by determinations, the combination force between the substrate and the coating was very good, the properties of coating to resist corrosion and abrasion were 4 times better than that of Ni-P alloy by the tests. The coating was finery in ornamentally also.

The study on combinatorial additives and plating technics for preparation and apply Ni-Co-P alloy coating was carried out completely, and the Ni-Co-P alloy with functional, corrosion-resistance and ornamental multicomponents was found, the optimum technics of plating multicomponents alloy was been found. The coating made in optimum technics was good in corrosion-resistance and wear-resistance, and with a smooth, fine, shining surface. It was proved by determinations that the 8.2% phosphorus in the coating and the coating was amorphous crystal. It was found that the combination force between the substrate and coating was very good, the corrosion-resistance and abrasion-resistance of coating were much better than that of Ni-P alloy according to the examination, the Ni-Co-P alloy coating with special character which were good magnetic properties and finery in ornamentally also.