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基于肿瘤微环境的黑色素瘤患者生存免疫评分指标

Immune Score Indicator for the Survival of Melanoma Patients Based on Tumor Microenvironment.

作者信息

Ning Xuchao, Li Renzhi, Zhang Bin, Wang Yue, Zhou Ziyi, Ji Zanzan, Lyu Xiajie, Chen Zhenyu

机构信息

Department of Cosmetic and Plastic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266072, People's Republic of China.

Dalian Medical University, Dalian, Liaoning, 116000, People's Republic of China.

出版信息

Int J Gen Med. 2021 Dec 30;14:10397-10416. doi: 10.2147/IJGM.S336105. eCollection 2021.

Abstract

BACKGROUND

Tumor microenvironment (TME) refers to the cellular environment where tumors exist, including immune cells, fibroblasts, stromal cells, chemokines, etc. TME is closely related to the prognosis of various tumors; nevertheless, limited studies have established predictive prognosis models based on TME. This work aims to construct a survival prediction model for melanoma patients based on TME.

METHODS

Data of 482 melanoma patients were extracted from The Cancer Genome Atlas (TCGA) database. Based on the infiltration of immune cells (Immune score), stromal cells (Stromal score), and tumor purity (Estimate score), the "Estimate" algorithm was used to construct 3 scores for each patient. To identify the differentially expressed genes (DEGs), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using DAVID database and visualized using the R software. The STRING database was used to construct the protein-protein interaction (PPI) network and functional modules. expression was confirmed via Western Blotting and quantitative reverse transcription PCR (RT-qPCR) analyses.

RESULTS

Patients with higher immune scores estimate scores showed better OS than those with lower scores. All three scores were related to age and primary tumor stage. Further, DEGs between patients with high immune/stromal scores and low immune/stromal scores were screened. Eventually, 10 down-regulated DEGs and 201 up-regulated DEGs were identified as TME associated genes. Out of these, the gene demonstrated close association with survival and was confirmed in the included melanoma patients.

CONCLUSION

In summary, TME is closely associated with the prognosis of melanoma patients. Besides, genes including promote the TME-mediated regulation of melanoma.

摘要

背景

肿瘤微环境(TME)是指肿瘤所处的细胞环境,包括免疫细胞、成纤维细胞、基质细胞、趋化因子等。TME与各种肿瘤的预后密切相关;然而,基于TME建立预测预后模型的研究有限。本研究旨在基于TME构建黑色素瘤患者的生存预测模型。

方法

从癌症基因组图谱(TCGA)数据库中提取482例黑色素瘤患者的数据。基于免疫细胞浸润(免疫评分)、基质细胞浸润(基质评分)和肿瘤纯度(估计评分),使用“估计”算法为每位患者构建3个评分。为了鉴定差异表达基因(DEG),使用DAVID数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,并使用R软件进行可视化。使用STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络和功能模块。通过蛋白质免疫印迹和定量逆转录PCR(RT-qPCR)分析确认 表达。

结果

免疫评分和估计评分较高的患者总生存期(OS)优于评分较低的患者。所有三个评分均与年龄和原发肿瘤分期相关。此外,筛选了高免疫/基质评分患者与低免疫/基质评分患者之间的DEG。最终,鉴定出10个下调的DEG和201个上调的DEG为TME相关基因。其中, 基因与生存密切相关,并在纳入的黑色素瘤患者中得到证实。

结论

总之,TME与黑色素瘤患者的预后密切相关。此外,包括 在内的基因促进了TME介导的黑色素瘤调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358e/8724722/1702a7e6c63f/IJGM-14-10397-g0001.jpg

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