Abstract
BackgroundsOsteosarcomas 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.MethodsThe 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.ResultsOS 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.ConclusionThese results could assist clinicians to select targets for immunotherapies and individualize treatment strategies for patients with OS.
Highlights
Osteosarcoma (OS), as the most common primary malignant tumor of bone, was frequently lethal via metastasis to the lung and primarily affected children and adolescents [1,2,3,4,5,6,7,8,9,10]
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
In addition to nine genes related to differences in immune cell infiltration in osteosarcoma, the above-mentioned genes in GO or/and KEGG terms might take effect on the biological process of OS
Summary
Osteosarcoma (OS), as the most common primary malignant tumor of bone, was frequently lethal via metastasis to the lung and primarily affected children and adolescents [1,2,3,4,5,6,7,8,9,10]. There is a second peak in incidence in those over the age of 50. Liu et al BMC Cancer (2021) 21:1345 approximately one to three cases annually per million. The 5-year survival rate for recurrent or metastatic OS is less than 25% [11, 12], though patients of OS can be typically treated with surgery and intensive adjuvant chemotherapy. The survival rate of patients with OS treated with surgery (mainstay of curative OS treatment) alone is approximately 15–17% [11, 13]. There is an urgent requirement to develop effective and safe potential future therapies for patients with OS, which exerts minimal cytotoxicity on healthy tissue [14,15,16,17,18,19,20,21,22,23,24,25]
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