Abstract
Background Serglycin (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 methods The 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.
Results The 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.
Conclusions SRGN (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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Zengcheng Zou, Yue Li, and Wenhai Guo are co-authors, 600 Tianhe Road, Guangzhou, Guangdong, China. Tel: +0086 020 85253497
Funding statement: Supported by Science and Technology Planning Project of Guangdong Province, China, no. 2017A030313738, 2022A1515011689
Figure 5 was added.Manuscript and supplementary were reivsed.