Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of osteosarcoma cancer

Abstract

Backgrounds Osteosarcomas are one of the most common primary malignant tumors of bone. It primarily occurs in children and adolescents, with the second highest incidence among people over 50 years old. Although there were immense improvements in the survival of patients with osteosarcoma in the past 30 years, targetable mutations and agents of osteosarcomas still have been generally not satisfactory. Therefore, it is of great importance to further explore the highly specialized immune environment of bone, genes related to macrophage infiltration and potential therapeutic biomarkers and targets. Methods The 11 expression data sets of OS tissues and the 11 data sets of adjacent non-tumorous tissues available in the GEO database GSE126209 were used to conduct immune infiltration analysis. Then, through WGCNA analysis, we acquired the co-expression modules related to Mast cells activated and performed the GO and KEGG enrichment analysis. Next, we did the survival prognosis analysis and plotted a survival curve. Finally, we analyzed the COX multivariate regression of gene expression on clinical parameters and drew forest maps for visualization by the forest plot package. Results OS disease-related immune cell populations, mainly Mast cells activated, have higher cell content (p = 0.006) than the normal group. Then, we identified co-expression modules related to Mast cells activated. In sum, a total of 822 genes from the top three strongest positive correlation module MEbrown4, MEdarkslateblue and MEnavajowhite2 and the strongest negative correlation module MEdarkturquoise. From that, we identified nine genes with different levels in immune cell infiltration related to osteosarcoma, eight of which including SORBS2, BAIAP2L2, ATAD2, CYGB, PAMR1, PSIP1, SNAPC3 and ZDHHC21 in their low abundance have higher disease-free survival probability than the group in their high abundances. Conclusion These results could assist clinicians to select targets for immunotherapies and individualize treatment strategies for patients with OS.

Dynamic Expression of Palmitoylation Regulators across Human Organ Development and Cancers Based on Bioinformatics

“…In addition, our results demonstrated that patients with a lower expression of ZDHHC7/20/21 showed worse survival in LIHC. Liu et al found that the group with lower ZDHHC21 expression levels has higher disease-free survival possibilities than those with high ZDHHC21 in OS [ 67 ]. Thus, these results implied that ZDHHC7/20/21 play oncogenic roles in cancer.…”

Tumor-Promoting ATAD2 and Its Preclinical Challenges

“…ATAD2 is not only tumorigenic but also associated with immune cell infiltration in the tumor microenvironment in osteosarcoma (OS). ATAD2, a downstream target of methyltransferase-like 3 (METTL3), is positively regulated by METTL3 and is a biomarker for predicting prognosis and a candidate target for diagnosis and treatment of OS [ 55 , 130 , 131 , 132 ]. ATAD2 is highly expressed and directly negatively regulated by miR-186 in retinoblastoma (RB).…”

Heparin and Heparin-Based Drug Delivery Systems: Pleiotropic Molecular Effects at Multiple Drug Resistance of Osteosarcoma and Immune Cells

“…The immunological environment of the OS consists mainly of T lymphocytes, macrophages, and other cell subpopulations, including B lymphocytes and mast cells. OS cells control the composition and differentiation of immune-infiltrating cells (e.g., the balance between M1 and M2 macrophage subtypes) and create a local immune tolerance environment that promotes tumor growth, MDR, and metastasis [ 9 ]. Tumor-associated macrophages (TAMs) and T lymphocytes are thought to be the main components of the immune environment in OS [ 84 ].…”

“…Osteosarcoma (OS) is an extremely aggressive, malignant mesenchymal bone tumor that arises from the malignancy of mesenchymal stem cells (MSCs) [ 4 ]. The formation and development of OS is also associated with immune infiltration and a very complex tumor microenvironment [ 5 , 6 ] OS is a rare tumor type that mainly affects young people and children [ 7 , 8 ], with the incidence of the disease increasing sharply after the age of 50 [ 9 ]. OS most commonly occurs in the distal femur and proximal tibia [ 10 , 11 ].…”