Exploration of gene expression profiles and immune microenvironment between high and low tumor mutation burden groups in prostate cancer
Exploration of gene expression profiles and immune microenvironment between high and low tumor mutation burden groups in prostate cancer
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DOI：
10.1016/j.intimp.2020.106709
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发表时间：
2020-09-01
影响因子：
5.6
通讯作者：
Chen, Lingwu
中科院分区：
文献类型：
--
作者：
Luo, Cheng;Chen, Junxing;Chen, Lingwu
背景：肿瘤突变负荷（TMB）已被确立为各种癌症对免疫治疗反应和预后的生物标志物。然而，TMB与前列腺癌（PCa）预后之间的关系仍不清楚。本研究旨在探讨TMB在生化复发（BCR）和高，低TMB group.Methods免疫微环境的影响：突变数据，基因表达，临床病理信息从癌症基因组图谱（TCGA）下载。鉴定突变类型和TMB值。以TMB中位数为分界点，将所有样本分为高TMB组和低TMB组。结果：TMB组中最常见的变异类型和SNV为单核苷酸多态性（SNP）和C> T。分别高TMB水平与年龄较大、淋巴结阳性、国际泌尿病理学会（ISUP）分级较高、分期较晚和无BCR生存率较差显著相关。共鉴定出132个DEG，它们参与受体配体活性和激素活性。6个核心基因UBE2C、PLK1、CDC20、BUB1、CDK1和HJURP的高表达与无BCR生存率差相关。免疫细胞浸润分析显示，活化的CD4（+）记忆性T细胞数量在高、低TMB组间存在显著差异。结论：本研究全面描述了PCa中突变和TMB相关DEG的概述。TMB与无BCR生存和免疫微环境中活化的CD4（+）记忆T细胞浸润相关。
Background: Tumor mutation burden (TMB) has been established as a biomarker for response to immune therapy and prognosis in various cancers. However, the association between TMB and prognosis of prostate cancer (PCa) remains unclear. This study aimed to investigate the impact of TMB in biochemical recurrence (BCR) and the immune microenvironment in high and low TMB groups.Methods: Mutation data, gene expression, clinicopathological information were downloaded from The Cancer Genome Atlas (TCGA). Mutation types and TMB values were identified. All samples were divided into high and low TMB groups with median TMB value as the cutoff point. The BCR-free survival rates, Differentially expressed genes (DEGs) and immune cells infiltrations in different TMB groups were identified.Results: The most common variant type and SNV were single nucleotide polymorphism and C > T. respectively. High TMB level was significantly associated with older age, positive lymph node, higher International Society of Urological Pathology (ISUP) grade, advanced stage and poor BCR-free survival. 132 DEGs were identified and involved in receptor ligand activity and hormone activity. High expression of six core genes UBE2C, PLK1, CDC20, BUB1, CDK1 and HJURP were associated with worse BCR-free survival. The analysis of immune cells infiltration revealed that the amount of activated CD4(+) memory T cells was significantly different in high and low TMB groups.Conclusions: The current study comprehensively described the summary of mutation and TMB related DEGs in PCa. TMB was associated with BCR-free survival and the infiltration of activated CD4(+) memory T cells in the immune microenvironment.