Based on our analysis and previous publications, the ECM depletion process (degradation of ECM components) in 5-FU-benefit GC patients could be possibly regulated through TME secreted protein HPSE, and the ECM enrichment process in 5-FU-futile patients could be possibly mediated through TME secreted proteins including LOX, WNT5A, LOXL2, ANGPT2, BMP1, PDGFB, ADAMTS9, IGLON5 and WNT7A (Figure 7). The gene discussed is LOXL2; the disease is gastric cancer.