As direct evidence, Shp−/− mice have increased levels of chemokines and cytokines in serum together with the activation of signal transducer and activator of transcription 3 and 5 (STAT3 and STAT5) inflammatory signaling pathways in the liver (our unpublished data) and develop spontaneous hepatocellular carcinomas at 12 to 15 months of age [52]. This evidence concerns the gene STAT3 and hepatocellular carcinoma.