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基于TCGA数据库的食管鳞状细胞癌ceRNA网络中与肿瘤微环境相关的预后生物标志物的鉴定：一项生物信息学研究

Identification of prognostic biomarkers associated with tumor microenvironment in ceRNA network for esophageal squamous cell carcinoma: a bioinformatics study based on TCGA database.

作者信息

Song Danlei, Wei Yongjian, Hu Yuping, Chen Xia, Zheng Ya, Liu Min, Wang Yuping, Zhou Yongning

机构信息

The First Clinical Medical College, Lanzhou University, Lanzhou, China.

Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, 730000, China.

出版信息

Discov Oncol. 2021 Nov 1;12(1):46. doi: 10.1007/s12672-021-00442-5.

DOI:10.1007/s12672-021-00442-5
PMID:35201503
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8777578/
Abstract

BACKGROUND

Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer in the world with high incidence rate and poor prognosis. Infiltrated immune and stromal cells are vital components of tumor microenvironment (TME) and have a significant impact on the progression of ESCC. The competitive endogenous RNA (ceRNA) hypothesis has been proved important in the molecular biological mechanisms of tumor development. However, there are few studies on the relationship between ceRNA and ESCC TME.

METHODS

The proportion of tumor-infiltrating immune cells and the amount of stromal and immune cells in ESCC cases were calculated from The Cancer Genome Atlas database using the CIBERSORT and ESTIMATE calculation methods. After stratified identification of differentially expressed genes, WGCNA and miRNA prediction system were applied to construct ceRNA network. Finally, PPI network and survival analysis were selected to discriminate prognostic signature. And the results were verified in two independent groups from Gene Expression Omnibus and Lanzhou, China.

RESULTS

We found that high Stromal and ESTIMATE scores were significantly associated with poor overall survival. Three TME-related key prognostic genes were screened, namely, LCP2, CD86, SLA. And the expression of them was significantly correlated with infiltrated immunocytes. It is also found that ESTIMATE Score and the expression of CD86 were both related to TNM system of ESCC.

CONCLUSIONS

We identified three novel TME-related prognostic markers and their lncRNA-miRNA-mRNA pathway in ESCC patients, which may provide new strategies for the targeted therapy.

摘要

背景

食管鳞状细胞癌（ESCC）是世界上最常见的食管癌组织学类型，发病率高且预后差。浸润的免疫细胞和基质细胞是肿瘤微环境（TME）的重要组成部分，对ESCC的进展有重大影响。竞争性内源RNA（ceRNA）假说已被证明在肿瘤发生的分子生物学机制中很重要。然而，关于ceRNA与ESCC TME之间关系的研究很少。

方法

使用CIBERSORT和ESTIMATE计算方法从癌症基因组图谱数据库中计算ESCC病例中肿瘤浸润免疫细胞的比例以及基质细胞和免疫细胞的数量。在对差异表达基因进行分层鉴定后，应用WGCNA和miRNA预测系统构建ceRNA网络。最后，选择蛋白质-蛋白质相互作用（PPI）网络和生存分析来鉴别预后特征。并在来自基因表达综合数据库和中国兰州的两个独立队列中验证结果。

结果

我们发现高基质评分和ESTIMATE评分与较差的总生存期显著相关。筛选出三个与TME相关的关键预后基因，即LCP2、CD86、SLA。它们的表达与浸润免疫细胞显著相关。还发现ESTIMATE评分和CD86的表达均与ESCC的TNM分期系统有关。

结论

我们在ESCC患者中鉴定出三个新的与TME相关的预后标志物及其lncRNA-miRNA-mRNA通路，这可能为靶向治疗提供新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa72/8777578/8eb35c0e4939/12672_2021_442_Fig13_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa72/8777578/94e8a1dd99ed/12672_2021_442_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa72/8777578/946cf689f629/12672_2021_442_Fig11_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa72/8777578/8eb35c0e4939/12672_2021_442_Fig13_HTML.jpg

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