To determine the relationship between G6PD and AKR1B10 and ECM stiffness in HCC, we performed immunohistochemical (IHC) validation in a matched cohort stratified by unconfined compression analysis-measured matrix stiffness and therapeutic response: 10 sorafenib-resistant patients with high ECM and 10 sorafenib-sensitive patients with low stiffness. The gene discussed is G6PD; the disease is hepatocellular carcinoma.