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探讨 T 细胞标记基因表达对肠型胃癌的病理生物学和临床预后结局的影响。

Exploring the Influence of T Cell Marker Gene Expression on the Pathobiology and Clinical Prognostic Outcomes in Intestinal-Type Gastric Carcinoma.

机构信息

Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 100 Huaihai Avenue, Hefei, 230012, Anhui, China.

School of Life Sciences, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.

出版信息

J Gastrointest Cancer. 2024 Sep;55(3):1410-1424. doi: 10.1007/s12029-024-01104-9. Epub 2024 Aug 13.

Abstract

BACKGROUND

Gastric cancer (GC) poses a significant global health challenge. This study is aimed at elucidating the role of the immune system, particularly T cells and their subtypes, in the pathogenesis and progression of intestinal-type gastric carcinoma (GC), and at evaluating the predictive utility of a T cell marker gene-based risk score for overall survival.

METHODS

We performed an extensive analysis using single-cell RNA sequencing data to map the diversity of immune cells and identify specific T cell marker genes within GC. Pseudotime trajectory analysis was employed to observe the expression patterns of tumor-related pathways and transcription factors (TFs) at various disease stages. We developed a risk score using data from The Cancer Genome Atlas (TCGA) as a training set and validated it with the GSE15459 dataset.

RESULTS

Our analysis revealed distinct patterns of T cell marker gene expression associated with different stages of GC. The risk score, based on these markers, successfully stratified patients into high-risk and low-risk groups with significantly different overall survival prospects. High-risk patients exhibited poorer survival outcomes compared to low-risk patients (p < 0.05). Additionally, the risk score was capable of identifying patients across a spectrum from chronic atrophic gastritis to early GC.

CONCLUSION

The findings enhance the understanding of the tumor immune microenvironment in GC and propose new immunotherapeutic targets. The T cell marker gene-based risk score offers a potential tool for gastroenterologists to tailor treatment plans more precisely according to the cancer's severity.

摘要

背景

胃癌(GC)是一个全球性的健康挑战。本研究旨在阐明免疫系统,特别是 T 细胞及其亚群,在肠型胃癌(GC)发病机制和进展中的作用,并评估基于 T 细胞标志物基因的风险评分对总生存期的预测价值。

方法

我们使用单细胞 RNA 测序数据进行了广泛的分析,以绘制免疫细胞的多样性图谱,并鉴定 GC 中特定的 T 细胞标志物基因。使用伪时间轨迹分析观察肿瘤相关途径和转录因子(TFs)在不同疾病阶段的表达模式。我们使用癌症基因组图谱(TCGA)的数据作为训练集开发了一个风险评分,并使用 GSE15459 数据集进行了验证。

结果

我们的分析揭示了与 GC 不同阶段相关的 T 细胞标志物基因表达的不同模式。基于这些标志物的风险评分成功地将患者分为高风险和低风险组,两组患者的总生存期存在显著差异。与低风险患者相比,高风险患者的生存结果较差(p<0.05)。此外,该风险评分能够识别从慢性萎缩性胃炎到早期 GC 患者的一系列患者。

结论

这些发现增强了对 GC 肿瘤免疫微环境的理解,并提出了新的免疫治疗靶点。基于 T 细胞标志物基因的风险评分为胃肠病学家提供了一种潜在的工具,根据癌症的严重程度更精确地制定治疗计划。

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