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Loss Of MHC Class I Related Gene Expression Inhibited The M1 Macrophages Infiltration In Tumor Microenvironment Of Ovarian Serous Cystadenocarcinoma
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Abstract
Background: Previous studies have shown that tumor immune microenvironment was an important factor affecting the progression and prognosis of ovarian cancer. The purpose of this study is to explore the prognosis related immune cell types in the immune microenvironment of ovarian cancer by using the ovarian cancer database, and to study the potential factors affecting specific immune cell infiltration. Method: Based on TCGA ovarian cancer database, CIBERSORT method was used to preliminarily analyze the infiltration ratios of 22 kinds of immune cells around ovarian cancer, and to further evaluate the correlation between infiltration cells and prognosis based on the survival data. In addition, this study will calculate the tumor infiltrating M1 Macrophages abundance (IM1A) to verify the correlation between M1 Macrophages load and the prognosis of ovarian cancer; and to explore the potential pathway of M1 Macrophages infiltration by Pearson correlation analysis. Results: The results showed that the infiltration proportion of follicular helper T cells and M1 Macrophases was negatively correlated with the poor prognosis of ovarian serous cystadenocarcinoma, while activated Mast cells was opposite. In addition, the overall survival of ovarian cancer patients with high IM1A was significantly longer than that of patients with low IM1A; the enrichment of GSEA KEGG pathway showed that multiple pathways were correlated with M1 Macrophages infiltration (including 67 positive and 1 negative pathways), and the highest correlation was found in antigen processing and presentation pathway. The expression level of some MHC class I related genes (potential target genes of immunotherapy) in antigen processing and presentation pathway was positively correlated with the infiltration ratios of M1 Macrophages in microenvironment, including HLA A, HLA B, HLA C, HLA E, HLA F, B2M, TAP1, TAP2, and TAPBP. Conclusion: In general, the decreased infiltration of M1 Macrophages indicates poor prognosis of ovarian serous cystadenocarcinoma, and the expression loss of MHC class I pathway gene might be the key factor for the inhibition of infiltration of M1 Macrophages. Altering these key genes expression could improve the infiltration of M1 Macrophages and the overall prognosis of ovarian serous cystadenocarcinoma.
Springer Science and Business Media LLC
Title: Loss Of MHC Class I Related Gene Expression Inhibited The M1 Macrophages Infiltration In Tumor Microenvironment Of Ovarian Serous Cystadenocarcinoma
Description:
Abstract
Background: Previous studies have shown that tumor immune microenvironment was an important factor affecting the progression and prognosis of ovarian cancer.
The purpose of this study is to explore the prognosis related immune cell types in the immune microenvironment of ovarian cancer by using the ovarian cancer database, and to study the potential factors affecting specific immune cell infiltration.
Method: Based on TCGA ovarian cancer database, CIBERSORT method was used to preliminarily analyze the infiltration ratios of 22 kinds of immune cells around ovarian cancer, and to further evaluate the correlation between infiltration cells and prognosis based on the survival data.
In addition, this study will calculate the tumor infiltrating M1 Macrophages abundance (IM1A) to verify the correlation between M1 Macrophages load and the prognosis of ovarian cancer; and to explore the potential pathway of M1 Macrophages infiltration by Pearson correlation analysis.
Results: The results showed that the infiltration proportion of follicular helper T cells and M1 Macrophases was negatively correlated with the poor prognosis of ovarian serous cystadenocarcinoma, while activated Mast cells was opposite.
In addition, the overall survival of ovarian cancer patients with high IM1A was significantly longer than that of patients with low IM1A; the enrichment of GSEA KEGG pathway showed that multiple pathways were correlated with M1 Macrophages infiltration (including 67 positive and 1 negative pathways), and the highest correlation was found in antigen processing and presentation pathway.
The expression level of some MHC class I related genes (potential target genes of immunotherapy) in antigen processing and presentation pathway was positively correlated with the infiltration ratios of M1 Macrophages in microenvironment, including HLA A, HLA B, HLA C, HLA E, HLA F, B2M, TAP1, TAP2, and TAPBP.
Conclusion: In general, the decreased infiltration of M1 Macrophages indicates poor prognosis of ovarian serous cystadenocarcinoma, and the expression loss of MHC class I pathway gene might be the key factor for the inhibition of infiltration of M1 Macrophages.
Altering these key genes expression could improve the infiltration of M1 Macrophages and the overall prognosis of ovarian serous cystadenocarcinoma.
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