364P Immune checkpoint gene expression differentiate immune-inflamed and immune-cold tumors in HPV-associated cervical squamous cell carcinoma

10-15% of all HCC cases and is associated with dismal prognoses, marked by early recurrence and reduced overall survival.MTM-HCC is notably linked to vascular invasion, advanced tumor stages, HBV infection, and elevated alpha-fetoprotein levels.A unique feature of MTM-HCC is its sinusoid-like microvascular pattern, "vessels that encapsulate tumor clusters" (VETC) pattern, which facilitates liver and distant organ metastasis.While TP53 mutations and FGF19 amplification have been identified in MTM-HCC, the precise mechanisms underlying its development remain elusive. Methods:The expression of TGF family was evaluated by RT-qPCR, and western blotting, using 30 cases of HCC and 23 cases of MTM-HCC patients tissues and cancer cells.To evaluate the functions of TGF2 in MTM-HCC, proliferation assays, invasion assays, drug resistance assays, spheroid formation analysis, western blot analysis, inhibitor assays, nuclear fractions, ubiquitination assays, and immunofluorescence microscopy analysis, tubule formation assays, RT-qPCR, and tumor cell spheroid coculture analysis were performed.Results: Our research reveals that TGF2 plays a pivotal role in shaping the characteristic traits of MTM-HCC, such as drug resistance, stemness, spheroid formation, enhanced invasion, and proliferation.Unlike TGF1, TGF2 triggers prolonged activation of the AKT signaling pathway, subsequently leading to GSK3 and -catenin activation.The activated -catenin, in turn, upregulates genes associated with EMT, cell proliferation, and notably, angiogenesis, including ANGPT2 and VEGF-165a.TGF2 exhibits a more pronounced impact on endothelial cell proliferation and migration compared to TGF1.Furthermore, TGF2 regulates genes associated with EndMT such as -SMA, Vimentin, and N-cadherin.Conclusions: TGF2 signaling is a critical underlying mechanism in the tumorigenesis of MTM-HCC, and targeting the TGF2 signaling pathway could offer a potential therapeutic approach for the treatment of MTM-HCC.