基于细胞免疫浸润调控的ceRNA网络,采用综合生物信息学分析与验证结果显示SOX12可能作为结肠腺癌的潜在生物标志物。
Integrated bioinformatics and validation reveal SOX12 as potential biomarker in colon adenocarcinoma based on an immune infiltration-related ceRNA network.
发表日期:2023 Sep 05
作者:
Xinyi Chen, Mu Yang, Jingyao Tu, Xianglin Yuan
来源:
GENES & DEVELOPMENT
摘要:
本研究的主要目标是构建竞争性内源性RNA(ceRNA)网络,并评估肿瘤浸润免疫细胞(TIICs)和ceRNA网络中关键生物标志物在结肠腺癌(COAD)患者中的预后意义。采用综合生物信息学工具筛选与COAD相关的差异表达基因(DEGs)、miRNA(DEMs)和lncRNA(DELs),从而创建ceRNA网络。采用CIBERSORT技术评估COAD中TIICs的意义,并进而建立免疫相关预后预测模型。进行共表达分析以确定ceRNA网络中的关键基因与免疫学上显著的TIICs之间的关系。本研究还利用了5个GEO数据集和基于网络的数据库对结果进行外部验证。研究发现了关键中心基因与免疫细胞之间的显著关系,通过共表达分析得出。两个中心调节因子(SOX12和H19)在ceRNA相关预后模型中显示出显著的预后价值,并且它们的表达水平升高在多种CRC细胞系中得到验证。此外,SOX12的沉默导致结肠癌细胞增殖、迁移和侵袭的抑制。通过构建ceRNA网络和评估TIICs,本研究成功建立了两个风险评分模型和评分表。这些模型作为理解分子过程和预测COAD患者预后的有价值工具。对SOX12和H19中心调节因子进行进一步验证,进一步证实它们在COAD中作为关键生物标志物的潜在作用。© 2023. 作者,独家许可给Springer-Verlag GmbH Germany,属于Springer Nature的一部分。
The primary objective of this study was to construct competing endogenous RNA (ceRNA) networks and evaluate the prognostic significance of tumor-infiltrating immune cells (TIICs) and key biomarkers within the ceRNA networks in colon adenocarcinoma (COAD) patients.Comprehensive bioinformatics tools were used to screen differentially expressed genes (DEGs), miRNAs (DEMs), and lncRNAs (DELs) related to COAD, leading to the creation of ceRNA networks. The CIBERSORT technique was employed to assess the significance of TIICs in COAD, and an immune-related prognosis prediction model was subsequently developed. Co-expression analyses were conducted to determine the relationship between key genes in ceRNA networks and immunologically significant TIICs. The study also utilized 5 GEO datasets and web-based databases to externally validate the findings.The study revealed a statistically significant relationship between key hub genes and immune cells, as determined through co-expression analysis. Two hub regulators (SOX12 and H19) demonstrated significant prognostic value in the ceRNA-related prognostic model, and their elevated expression levels were verified across multiple CRC cell lines. Additionally, the knockdown of SOX12 led to a suppression of proliferation, migration, and invasion in colon cancer cells.Through the construction of ceRNA networks and evaluation of TIICs, the study successfully established two risk score models and nomograms. These models serve as valuable tools for understanding the molecular processes and predicting the prognosis of COAD patients. Further validation of hub regulators SOX12 and H19 substantiates their potential role as key biomarkers in COAD.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.