CCN2 and cancer: Using spatial multi-omics technology, a novel subpopulation of cancer-associated fibroblasts (F5-CAF, marked by COL1A2/COL4A1/CTGF/FSTL1) was identified in HCC, which is spatially located around tumor nests and co-localizes with cancer cells exhibiting high stemness, driving liver cancer progression and poor prognosis by facilitating the existence of cancer stem cells (61).