Zhang Shupeng, Li Zhaojin, Hu Gang, Chen Hekai
Department of General Surgery, Tianjin Fifth Central Hospital, No. 41 Zhejiang Road, Binhai New Area, Tianjin, 300450, China.
Medical School of Tianjin University, No. 22, Tixiangting Road, Heping District, Tianjin, 300070, China.
Discov Oncol. 2025 Jan 17;16(1):57. doi: 10.1007/s12672-025-01798-8.
Gastric cancer (GC), a prevalent malignancy worldwide, encompasses a multitude of biological processes in its progression. Recently, ferroptosis, a novel mode of cell demise, has become a focal point in cancer research. The microenvironment of gastric cancer is composed of diverse cell populations, yet the specific gene expression profiles and their association with ferroptosis are not well understood. Our study employed single-cell RNA sequencing to thoroughly investigate the transcriptomic profiles and identify differential gene expression in gastric cancer, offering fresh insights into the cellular diversity and underlying molecular mechanisms of this disease. We discovered a set of significantly differentially expressed genes in GC, which may serve as valuable leads for future functional investigations. Subsequent analyses, including gene set intersection and functional enrichment, pinpointed genes implicated in ferroptosis and conducted comprehensive Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to elucidate their biological roles. In the gene selection and model validation section, critical genes were identified using machine learning algorithms, constructing a model with high predictive accuracy. Besides, distorted immune landscapes were further identified in RBL using ssGSEA analysis such that the complex association of gene expression features and its interaction networks as well as infiltration by various types of immune cells can be more clearly understood. Correlation analysis with different immune cell subtypes showed CTSB as an important regulator in the distributions of cancer infiltrating cells. Single-cell RNA sequencing analysis was utilized to map the cellular composition and gene expression profiles of cells in the gastric cancer microenvironment, which provide critical information for elucidating cellular heterogeneity as well as tumor microenvironment regulation in GC. Moreover, the distribution of FTH1, ZFP36 and CIRBP at different expression levels show new research prospects for functional information of these promoters in tumor microenvironment. In summary, the present study augments our knowledge of molecular mechanisms underlying gastric tumorigenesisa and provide scientific basis for identifing new targets and biomarkers in therapeutic diagnosis.
胃癌（GC）是一种在全球范围内普遍存在的恶性肿瘤，其进展涉及多种生物学过程。最近，铁死亡作为一种新的细胞死亡模式，已成为癌症研究的焦点。胃癌的微环境由多种细胞群体组成，但其特定的基因表达谱及其与铁死亡的关联尚未完全明确。我们的研究采用单细胞RNA测序技术，全面探究胃癌的转录组图谱并识别差异基因表达，为深入了解该疾病的细胞多样性和潜在分子机制提供了新的见解。我们在胃癌中发现了一组显著差异表达的基因，这些基因可能为未来的功能研究提供有价值的线索。随后的分析，包括基因集交集和功能富集分析，确定了与铁死亡相关的基因，并进行了全面的基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析，以阐明它们的生物学作用。在基因选择和模型验证部分，使用机器学习算法鉴定关键基因，构建了具有高预测准确性的模型。此外，通过单样本基因集富集分析（ssGSEA）进一步识别了RBL中扭曲的免疫格局，从而更清晰地了解基因表达特征及其相互作用网络的复杂关联以及各种免疫细胞的浸润情况。与不同免疫细胞亚型的相关性分析表明，组织蛋白酶B（CTSB）是癌症浸润细胞分布中的重要调节因子。利用单细胞RNA测序分析绘制了胃癌微环境中细胞的组成和基因表达谱，为阐明胃癌中的细胞异质性以及肿瘤微环境调控提供了关键信息。此外，不同表达水平下FTH1、ZFP36和CIRBP的分布为这些启动子在肿瘤微环境中的功能信息提供了新的研究前景。总之，本研究加深了我们对胃癌发生分子机制的认识，并为在治疗诊断中识别新靶点和生物标志物提供了科学依据。
