Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma
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RIMARY RESEARCH
Cancer Cell International Open Access
Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma Naiqiang Zhu and Jingyi Hou*
Abstract Background: Sarcomas, cancers originating from mesenchymal cells, are comprehensive tumors with poor prognoses, yet their tumorigenic mechanisms are largely unknown. In this study, we characterize infiltrating immune cells and analyze immune scores to identify the molecular mechanism of immunologic response to sarcomas. Method: The “CIBERSORT” algorithm was used to calculate the amount of L22 immune cell infiltration in sarcomas. Then, the “ESTIMATE” algorithm was used to assess the “Estimate,” “Immune,” and “Stromal” scores. Weighted gene coexpression network analysis (WGCNA) was utilized to identify the significant module related to the immune therapeutic target. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the “clusterProfiler” package in R for annotation and visualization. Results: Macrophages were the most common immune cells infiltrating sarcomas. The number of CD8 T cells was negatively associated with that of M0 and M2 macrophages, and positively associated with M macrophages in sarcomas samples. The clinical parameters (disease type, gender) significantly increased with higher Estimate, Immune, and Stromal scores, and with a better prognosis. The blue module was significantly associated with CD8 T cells. Functional enrichment analysis showed that the blue module was mainly involved in chemokine signaling and the PI3K-Akt signaling pathway. CD48, P2RY10 and RASAL3 were identified and validated at the protein level. Conclusion: Based on the immune cell infiltration and immune microenvironment, three key genes were identified, thus presenting novel molecular mechanisms of sarcoma metastasis. Keywords: Sarcomas, Immune infiltration, Prognosis, Weighted gene co-expression analysis, Tumor microenvironment Background Sarcomas are a widespread, heterogeneous group of tumors that occur on the skin, under the skin, in the periosteum, and on the ends of the long bones of adolescents and the elderly (overall incidence: 1–2/100,000 annually) [1], which is characteristic of cancers originating from mesenchymal cells [2]. Histopathologically, sarcomas are
*Correspondence: [email protected] Department of Minimally Invasive Spinal Surgery, Affiliated Hospital of Chengde Medical College, Chengde 067000, China
classified as either bone or soft tissue sarcomas [3]. To date, the etiology of sarcomas is not well characterized; however, their incidence appears to be associated with heredity [4], viral infection [5], trauma [6], environmental factors [7], and exposure to radiation [8]. Compared with other cancers, the degree of malignancy of sarcomas is relatively high [9], and hematogenous metastasis can spread to various organs, such as lung, brain, liver, and bone [10, 11]. Since sarcomas rarely display clinical manifestations in the initial stages of the disea
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