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通过单细胞测序和批量数据分析解析鞘脂代谢在食管癌免疫微环境和预后中的作用

Deciphering the role of sphingolipid metabolism in the immune microenvironment and prognosis of esophageal cancer via single-cell sequencing and bulk data analysis.

作者信息

He Rongzhang, Tang Jing, Lai Haotian, Zhang Tianchi, Du Linjuan, Wei Siqi, Zhao Ping, Tang Guobin, Liu Jie, Luo Xiufang

机构信息

Gastroenterology Department, Guangyuan Central Hospital, Guangyuan, China.

School of Clinical Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, China.

出版信息

Discov Oncol. 2024 Sep 27;15(1):505. doi: 10.1007/s12672-024-01379-1.

Abstract

BACKGROUND

Esophageal squamous cell carcinoma (ESCC) stands as a significant global health challenge, distinguished by its aggressive progression from the esophageal epithelium. Central to this malignancy is sphingolipid metabolism, a critical pathway that governs key cellular processes, including apoptosis and immune regulation, thereby influencing tumor behavior. The advent of single-cell and transcriptome sequencing technologies has catalyzed significant advancements in oncology research, offering unprecedented insights into the molecular underpinnings of cancer.

METHODS

We explored sphingolipid metabolism-related genes in ESCC using scRNA-seq data from GEO and transcriptome data from TCGA. We assessed 97 genes in epithelial cells with AUCell, UCell, and singscore algorithms, followed by bulk RNA-seq and differential analysis to identify prognosis-related genes. Immune infiltration and potential immunotherapeutic strategies were also investigated, and tumor gene mutations and drug treatment strategies were analyzed.

RESULT

Our study identified distinct gene expression patterns, highlighting ARSD, CTSA, DEGS1, and PPTQ's roles in later cellular stages. We identified seven independent prognostic genes and created a precise nomogram for prognosis.

CONCLUSION

This study integrates single-cell and transcriptomic data to provide a reliable prognostic model associated with sphingolipid metabolism and to inform immunotherapy and pharmacotherapy for ESCC at the genetic level. The findings have significant implications for precision therapy in esophageal cancer.

摘要

背景

食管鳞状细胞癌(ESCC)是一项重大的全球健康挑战,其特点是从食管上皮开始侵袭性进展。鞘脂代谢是这种恶性肿瘤的核心,这是一个关键途径,控制着包括细胞凋亡和免疫调节在内的关键细胞过程,从而影响肿瘤行为。单细胞和转录组测序技术的出现推动了肿瘤学研究的重大进展,为癌症的分子基础提供了前所未有的见解。

方法

我们使用来自GEO的scRNA-seq数据和来自TCGA的转录组数据,探索了ESCC中与鞘脂代谢相关的基因。我们使用AUCell、UCell和singscore算法评估了上皮细胞中的97个基因,随后进行批量RNA-seq和差异分析以确定预后相关基因。还研究了免疫浸润和潜在的免疫治疗策略,并分析了肿瘤基因突变和药物治疗策略。

结果

我们的研究确定了不同的基因表达模式,突出了ARSD、CTSA、DEGS1和PPTQ在后期细胞阶段的作用。我们确定了七个独立的预后基因,并创建了一个精确的预后列线图。

结论

本研究整合了单细胞和转录组数据,以提供与鞘脂代谢相关的可靠预后模型,并在基因水平上为ESCC的免疫治疗和药物治疗提供信息。这些发现对食管癌的精准治疗具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e23/11436545/5014673fc74e/12672_2024_1379_Fig1_HTML.jpg

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