Important Role of Hematopoietic Proteoglycan Serglycin in Liver Hepatocellular Carcinoma Associated with Tumor Microenvironment

Abstract

BackgroundSerglycin (SRGN) is a prominent hematopoietic proteoglycan and regulates tumorigenesis in malignancies. However, the role of serglycin is unclear in pan-cancer, especially liver hepatocellular cancer (LIHC).Materials and methodsThe expression and prognostic potential of SRGN in LIHC and other pan-cancer was investigated using the bioinformatics databases PrognoScan, GEPIA, Kaplan-Meier Plotter, and TIMER. HepG2 cells were transfected with a SRGN overexpressing vector. Proliferation, invasion, sorafenib resistance, and vasculature were examined in vitro. A subcutaneous xenograft tumor was constructed in nude mice.ResultsThe prognostic potential of SRGN was inconsistent in pan-cancer. The Kaplan-Meier Plotter indicated that SRGN expression was a favorable prognostic factor correcting for stage, grade, AJCC_T stage, sex, race, alcohol consumption, hepatitis virus infection, and sorafenib treatment in liver cancer. TIMER 2.0 showed that T cells CD8+, macrophage M1, macrophage M2, and endothelial cells(ECs) were strongly correlated with SRGN mRNA expression (r=0.552, P=5.79e-29; r=0.517, P=5.84e-25; r=0.696, P=3.26e51; and r=0.522, P=1.67e-25, respectively), and had prognostic potential in LIHC in the cohort with low or high levels of SRGN (HR=0.53, P=0.048; HR=3.09, P=0.00633; HR=1.99, P=0.0366; and HR=0.364, P=0.00638, respectively). SRGN promoted HepG2 cell in vitro and vivo proliferation, weak sorafenib resistance, invasion, and vasculature. CD206 and CD80 were up-regulated and down-regulated, respectively in subcutaneous tumor tissues.ConclusionsThe prognostic potential of serglycin is limited in LIHC. However, the pro-tumorigenic properties of SRGN and its closely association with tumor microenvironment cells may contribute to the development of new treatment strategies.