Abstract
BackgroundOvarian cancer is the leading cause of death among gynecological malignancies. Immunotherapy has demonstrated potential effects in ovarian cancer. However, few studies on immune-related prognostic signatures in ovarian cancer have been reported. This study aimed to identify hub genes associated with immune infiltrates to provide insight into the immune regulatory mechanisms in ovarian cancer.MethodsRaw data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and University of California, Santa Cruz (UCSC) Xena websites. Single-sample gene set enrichment analysis (ssGSEA) and weighted gene co-expression network analysis (WGCNA) were used to identify hub genes. Kaplan-Meier analysis and differential expression analysis were applied to explore the real hub genes.ResultsThrough ssGSEA and WGCNA, 7 hub genes (LY9, CD5, CXCL9, IL2RG, SLAMF1, SLAMF6, and SLAMF7) were identified. Finally, LY9 and SLAMF1 were recognized as the real hub genes in immune infiltrates of ovarian cancer. LY9 and SLAMF1 are classified as SLAM family receptors involved in the activation of hematopoietic cells and the pathogenesis of multiple malignancies. Furthermore, 12 lncRNAs and 43 miRNAs significantly related to the 2 hub genes were applied to construct a lncRNA-miRNA-mRNA ceRNA network. The lncRNA-miRNA-mRNA ceRNA network shows upstream regulatory sites of the 2 hub genes.ConclusionsThese findings improve our understanding of the regulatory mechanism of and reveal potential immune checkpoints for immunotherapy for ovarian cancer.
Highlights
Ovarian cancer is the leading cause of death among gynecological malignancies
Pathway enrichment analysis According to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, our results demonstrated that these hub genes are mainly involved in the following pathways: cytokine−cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, T cell receptor signaling pathway and primary immunodeficiency (Fig. 5A)
A long noncoding RNAs (lncRNAs)-miRNA-messenger RNAs (mRNAs) competing endogenous RNA (ceRNA) network is constructed During the following step, we found that 43 experimentally validated miRNAs had relationships with the 2 hub genes
Summary
Ovarian cancer is the leading cause of death among gynecological malignancies. Immunotherapy has demonstrated potential effects in ovarian cancer. Ovarian cancer is the leading cause of death among gynecological neoplasms [1]. Cytoreductive surgery followed by platinum-based chemotherapy is the standard treatment for advanced ovarian cancer. Most patients experience recurrence and eventually die. Angiogenesis inhibitors such as bevacizumab and PARP inhibitors have been recently added to the available. Less than 15% of patients with advanced/metastatic ovarian cancer respond to immune checkpoint inhibitors [2, 3]. In other words, this toxic and costly treatment is potentially ineffective in the majority of ovarian cancer patients.
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