Other links include findings that WNT3A expression is frequently deregulated in HCC 44, ALX3 is differentially expressed and methylated in TCGA LIHC data 45, and expression of NR1I2 (a transcription factor that regulates CYP3A4, a xenobiotic metabolizing enzyme whose substrates include both sorafenib and regorafenib) is linked to sorafenib resistance in late stage HCC 46. This evidence concerns the gene CYP3A4 and hepatocellular carcinoma.