SAMD9 Is Relating With M2 Macrophage and Remarkable Malignancy Characters in Low-Grade Glioma.

Wenping Ma,Tao Jiang,Kenan Zhang,Ying Zhang,Zhaoshi Bao

doi:10.3389/fimmu.2021.659659

Abstract

Immunoreactions regulated by TAMs (Tumor-associated macrophages) play a pivotal role in tumorigenesis and metastasis. In recent decades, treatments based on immune regulation have achieved revolutionary breakthroughs in cancer targeted therapies. The phenotypes of TAMs in gliomas are more heterogeneous and inherently complex than can be simply defined by classification into the M1 and M2 polarized states. The detailed mechanisms surrounding infiltrating macrophage phenotype and glioma characteristics remain undefined. SAMD9 (Sterile Alpha Motif Domain-Containing Protein 9) was found to be highly expressed in glioma and closely related to histological and genetic features in CGGA and TCGA databases. Simultaneously, we present evidence to show that there was a positive association between SAMD9 and malignancy characters in LGG. Univariable and Multivariate proportional hazard Cox analysis showed that SAMD9 was an independent prognostic factor for LGG. Surprisingly, Gene Ontology (GO) analysis showed SAMD9 expression level was remarkably well correlated with immunological responses and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis supported the connection with immune responses and tumorigenesis. Immune infiltration analysis demonstrated that high SAMD9 expression resulted in an accumulation of macrophages by CIBERSORT and TIMER databases, especially positively related to macrophage total marker gene AIF1 and Macrophage M2 marker gene CD163. IHC staining further indicated a high correlation of SAMD9 with those specific macrophage markers in the immune response. Human THP-1 cells were induced into M2 macrophages, which were then co-cultured with LN229 cells. Silencing of SAMD9 by shRNA in LN229 cells attenuated the infiltration abilities of M2 macrophage. SAMD9 explored immune response via relating of M2 macrophage in vitro. Our results revealed SAMD9 acted as the malignancy characters in LGG, enrichment with M2 macrophage.

Highlights

Glioma is a kind of tumor originates from glial cells or precursor cells [1,2,3]
The alkylating drug TMZ is routinely used for chemotherapy in glioma patients and MGMT promoter status was identified as a useful predictive biomarker for TMZ efficacy [42]
This information is highly consistent across the CGGA database 1 and TCGA databases (Figure 1D). These results indicated that lower expression of SAMD9 may be correlated with better prognosis of gliomas. we achieved the same tendency characters of SAMD9 in CGGA database 2 (Supplementary Figure 1)

Summary

Introduction

Glioma is a kind of tumor originates from glial cells or precursor cells [1,2,3] It is the most common type of primary tumors in the central nervous system [4,5,6]. The standard treatment for gliomas consisted of total tumor surgical resection, followed by radiotherapy and concurrent chemotherapy with TMZ (temozolomide) [7,8,9]. Using those comprehensive complex treatments, the overall survival achieved in glioma is not more than around 15 months, indicating the need for new innovative treatments which anchor the character and heterogeneity of glioma and expose the potential vital factors affecting tumorigenesis [6]. It was urgent and important to search for immune-related targets in gliomas

Methods

Results

Conclusion