Comprehensive Analysis of Tumor Microenvironment Identified Prognostic Immune-Related Gene Signature in Ovarian Cancer

被引:16
|
作者
Li, Na [1 ,2 ,3 ]
Li, Biao [1 ,2 ,3 ]
Zhan, Xianquan [1 ,2 ,3 ,4 ,5 ]
机构
[1] Shandong First Med Univ, Sci & Technol Innovat Ctr, Jinan, Peoples R China
[2] Cent South Univ, Xiangya Hosp, Minist Hlth, Key Lab Canc Prote Chinese, Changsha, Peoples R China
[3] Cent South Univ, Xiangya Hosp, State Local Joint Engn Lab Anticanc Drugs, Changsha, Peoples R China
[4] Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha, Peoples R China
[5] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China
关键词
ovarian cancer; immune-related-gene-signature; clinical characteristics; distribution of immune cells; distribution of tumor mutation burden;
D O I
10.3389/fgene.2021.616073
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background Accumulating evidence demonstrated that tumor microenvironmental cells played important roles in predicting clinical outcomes and therapeutic efficacy. We aimed to develop a reliable immune-related gene signature for predicting the prognosis of ovarian cancer (OC). Methods Single sample gene-set enrichment analysis (ssGSEA) of immune gene-sets was used to quantify the relative abundance of immune cell infiltration and develop high- and low-abundance immune subtypes of 308 OC samples. The presence of infiltrating stromal/immune cells in OC tissues was calculated as an estimate score. We estimated the correlation coefficients among the immune subtype, clinicopathological feature, immune score, distribution of immune cells, and tumor mutation burden (TMB). The differentially expressed immune-related genes between high- and low-abundance immune subtypes were further used to construct a gene signature of a prognostic model in OC with lasso regression analysis. Results The ssGSEA analysis divided OC samples into high- and low-abundance immune subtypes based on the abundance of immune cell infiltration, which was significantly related to the estimate score and clinical characteristics. The distribution of immune cells was also significantly different between high- and low-abundance immune subtypes. The correlation analysis showed the close relationship between TMB and the estimate score. The differentially expressed immune-related genes between high- and low-abundance immune subtypes were enriched in multiple immune-related pathways. Some immune checkpoints (PDL1, PD1, and CTLA-4) were overexpressed in the high-abundance immune subtype. Furthermore, the five-immune-related-gene-signature prognostic model (CCL18, CXCL13, HLA-DOB, HLA-DPB2, and TNFRSF17)-based high-risk and low-risk groups were significantly related to OC overall survival. Conclusion Immune-related genes were the promising predictors of prognosis and survival, and the comprehensive landscape of tumor microenvironmental cells of OC has potential for therapeutic schedule monitoring.
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页数:17
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