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CXCL13, FCRLA, PLA2G2D and MS4A1 Were Identified As Prognostic Biomarkers and Correlated with Immune Infiltration in Ovarian Cancer by Integrating TMB and Microenvironment Analysis
31 Pages Posted: 16 Jan 2020
More...Abstract
Background: The six most common malignancies in the world include ovarian cancer (OC), which is a severe tumor that seriously threatens women's lives. And it’s also one of the leading causes of death of patients with various gynecological tumors. Although many papers have reported that high TMB can generate many neoantigens to incited anti-tumor immune response and the immune infiltration degree of the tumor has an essential influence on prognosis, the interrelationship between TMB and immune scores in OC and its effect on prognosis were not examined systematically. Under this circumstance, our current study aims to discover the novel biomarkers in OC, and seek to investigate the role of hub genes in OC.
Results: We divided OC cases into two groups: the low tumor mutational burden (TMB) group and the high TMB group hinged on the somatic mutation data from the Cancer Genome Atlas (TCGA). Our researches found that the higher TMB, the better the survival prognosis of ovarian cancer. And we also categorized OC cases into low immune scores group and high immune scores group based on ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm from TCGA. It’s shown that the B cells naive, macrophages M0, and dendritic cells activated tended to be down-regulated in the low immune scores group, and the T cells CD8, T cells CD4 memory activated, and macrophages M2 tended to be up-regulated in the high immune scores group. To better explain the effects of TMB and the genes involved in immune cells on prognosis, we filtrated differential expression genes (DEGs) whose expression considerably linked to prognosis in OC patients. In addition, we analyzed Up-DGEs (Up-regulated DEGs) and Down-DEGs (Down-regulated DEGs) and then screened the top ten small-molecule drugs in CMap (ConnectivityMap), six candidate small molecule drugs were identified that are closely related to the clinical treatment of OC. Meanwhile, our researches further demonstrated that Up-DEGs were mainly involved in immune response and T cell proliferation by functional enrichment analysis and protein‐protein interaction (PPI) network. Finally, we validated these genes from the Group on Earth Observations (GEO) which included CXCL13, FCRLA, PLA2G2D and MS4A1.
Funding Statement: Contributions received from the TCGA network, the GTEx network and the CCLE Network. This study was supported by grants from the National Natural Science Foundation of China (No. 81572900). The Fundamental Research Funds for the Central Universities of Central South University (No. 502221804).
Declaration of Interests: The authors declare that they have no competing interests.
Ethics Approval Statement: Not required.
Keywords: ovarian cancer, TMB, immune scores, survival prognosis
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