Important Role of Hematopoietic Proteoglycan Serglycin in Liver Hepatocellular Carcinoma Associated with Tumor Microenvironment
- Publicado
- Servidor
- bioRxiv
- DOI
- 10.1101/2022.06.15.495916
Background
Serglycin (SRGN) is a prominent hematopoietic proteoglycan that regulates tumorigenesis; however, its role in tumor immunity is unclear.
Materials and methods
We investigated the expression and prognostic potential of SRGN in liver hepatocellular cancer (LIHC) in the context of pan-cancer (for showing the similarity and heterogeneity) using the PrognoScan, GEPIA, Kaplan–Meier Plotter, and TIMER bioinformatics databases. HepG2 cells were transfected with an SRGN over-expression vector, and their proliferation, invasion, sorafenib resistance, and vasculature were examined in vitro . A subcutaneous xenograft tumor model was created in nude mice.
Results
SRGN expression was prominent in M2 macrophages in LIHC. The Kaplan–Meier Plotter indicated that SRGN RNA was a favorable prognostic factor after correcting for clinical factors. TIMER 2.0 showed that the immune infiltrates of CD8+ T cells, M1 and M2 macrophages, and endothelial cells were strongly correlated with SRGN RNA expression (r=0.552, P=5.79e -29 ; r=0.517, P=5.84e -25 ; r=0.696, P=3.26e 51 ; and r=0.522, P=1.67e -25 , respectively), and had prognostic potential in LIHC in patients with low or high levels of SRGN, in addition to resting memory CD4+ T cells, hematopoietic stem cells (HSCs), and myeloid-derived suppressor cells (MDSCs). SRGN promoted the proliferation of HepG2 cells in vitro and in vivo , and was associated with weak sorafenib resistance, invasion, and vasculature. CD206 and CD80 were up-regulated and down-regulated, respectively, in subcutaneous tumor tissues.
Conclusions
The results comprehensively revealed relationships between SRGN and tumor microenvironment(TME)-infiltrating cells, especially monocyte/macrophage subsets. These may constitute an important TME because the pro-tumorigenicity of SRGN in liver cancer.