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食管鳞状细胞癌中 N6-甲基腺苷的单细胞图谱绘制及免疫浸润风险模型的探索。

Single-cell mapping of N6-methyladenosine in esophageal squamous cell carcinoma and exploration of the risk model for immune infiltration.

机构信息

Tumor Research and Therapy Center, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.

Shandong First Medical University, College of Basic Medicine, Shandong First Medical University-Shandong Academy of Medical Sciences, Jinan, Shandong, China.

出版信息

Front Endocrinol (Lausanne). 2023 Mar 21;14:1155009. doi: 10.3389/fendo.2023.1155009. eCollection 2023.

DOI:10.3389/fendo.2023.1155009
PMID:37025404
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10070687/
Abstract

BACKGROUND

N6-methyladenosine (m6A) modification is the most common RNA modification, but its potential role in the development of esophageal cancer and its specific mechanisms still need to be further investigated.

METHODS

Bulk RNA-seq of 174 patients with esophageal squamous carcinoma from the TCGA-ESCC cohort, GSE53625, and single-cell sequencing data from patients with esophageal squamous carcinoma from GSE188900 were included in this study. Single-cell analysis of scRNA-seq data from GSE188900 of 4 esophageal squamous carcinoma samples and calculation of PROGENy scores. Demonstrate the scoring of tumor-associated pathways for different cell populations. Cell Chat was calculated for cell populations. thereafter, m6A-related differential genes were sought and risk models were constructed to analyze the relevant biological functions and impact pathways of potential m6A genes and their impact on immune infiltration and tumor treatment sensitivity in ESCC was investigated.

RESULTS

By umap downscaling analysis, ESCC single-cell data were labelled into clusters of seven immune cell classes. Cellchat analysis showed that the network interactions of four signaling pathways, MIF, AFF, FN1 and CD99, all showed different cell type interactions. The prognostic risk model constructed by screening for m6A-related differential genes was of significant value in the prognostic stratification of ESCC patients and had a significant impact on immune infiltration and chemotherapy sensitivity in ESCC patients.

CONCLUSION

In our study, we explored a blueprint for the distribution of single cells in ESCC based on m6A methylation and constructed a risk model for immune infiltration analysis and tumor efficacy stratification in ESCC on this basis. This may provide important potential guidance for revealing the role of m6A in immune escape and treatment resistance in esophageal cancer.

摘要

背景

N6-甲基腺苷(m6A)修饰是最常见的 RNA 修饰,但它在食管癌发展中的潜在作用及其具体机制仍需进一步研究。

方法

本研究纳入了 TCGA-ESCC 队列的 174 例食管鳞癌患者的 bulk RNA-seq、GSE53625 和 GSE188900 中食管鳞癌患者的单细胞测序数据。对来自 GSE188900 的 4 例食管鳞癌样本的 scRNA-seq 数据进行单细胞分析,并计算 PROGENy 评分。展示不同细胞群体肿瘤相关途径的评分。计算细胞 Chat 用于细胞群体。之后,寻找 m6A 相关差异基因,并构建风险模型,分析潜在 m6A 基因的相关生物学功能和影响途径及其对 ESCC 免疫浸润和肿瘤治疗敏感性的影响。

结果

通过 umap 降维分析,ESCC 单细胞数据被标记为七个免疫细胞类别的聚类。Cellchat 分析表明,MIF、AFF、FN1 和 CD99 四个信号通路的网络相互作用均显示出不同的细胞类型相互作用。通过筛选 m6A 相关差异基因构建的预后风险模型,对 ESCC 患者的预后分层具有显著价值,并对 ESCC 患者的免疫浸润和化疗敏感性有显著影响。

结论

在本研究中,我们基于 m6A 甲基化探索了 ESCC 中单细胞分布的蓝图,并在此基础上构建了免疫浸润分析和 ESCC 肿瘤疗效分层的风险模型。这可能为揭示 m6A 在食管癌免疫逃逸和治疗耐药中的作用提供重要的潜在指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f9c/10070687/63ed8d9bd6c1/fendo-14-1155009-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f9c/10070687/5e4826110ae9/fendo-14-1155009-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f9c/10070687/63ed8d9bd6c1/fendo-14-1155009-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f9c/10070687/5e4826110ae9/fendo-14-1155009-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f9c/10070687/b92163e87e7c/fendo-14-1155009-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f9c/10070687/63ed8d9bd6c1/fendo-14-1155009-g007.jpg

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