Serglycin: the Role in Liver Hepatocellular Carcinoma shown by Bioinformatics and Association with Tumor Microenvironment

Abstract

AbstractBackgroundSerglycin (SRGN) is a prominent hematopoietic proteoglycan and regulates tumorigenesis in malignancies. However, the role of serglycin is unclear in liver hepatocellular cancer (LIHC).Materials and methodsThe expression and prognostic potential of SRGN in pan-cancer was investigated using the bioinformatics databases PrognoScan, GEPIA, Kaplan-Meier Plotter, and TIMER, etc. HepG2 cells were transfected with a SRGN over expressing vector. Proliferation, invasion, sorafenib resistance, and vasculature were examined in vitro. A subcutaneous xenograft tumor was constructed in nude mice.ResultsThe expression and prognostic potential of SRGN was inconsistent in pan-cancer. SRGN expressing in Macrophages.M2 instead of neutrophils was prominent 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 T cells CD8+, macrophage M1, macrophage M2, and endothelial cells(ECs) 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=3.26e51; 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 in addition to T cell CD4+ memory resting, hematopoietic stem cells (HSCs) and myeloid-derived suppressor cells (MDSCs). SRGN promoted in vitro and vivo proliferation of HepG2 cell, weak sorafenib resistance, invasion, and vasculature. CD206 and CD80 were up-regulated and down-regulated, respectively in subcutaneous tumor tissues.ConclusionsSRGN (serglycin) may have binary function on tumorigenesis. The prognostic potential of SRGN was associated with infiltrating cells of tumor microenvironment including monocyte/macrophage subsets, T cell CD8+, T cell CD4+ memory resting, ECs, HSCs and MDSCs in LIHC.