胃癌免疫亚型和预后模型：衰老相关基因分析的启示

IF 0.8 4区医学 Q4 IMMUNOLOGY

Critical Reviews in Immunology Pub Date : 2024-01-01 DOI:10.1615/critrevimmunol.2024052391

Jian Shen, Minzhe Li

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引用次数: 0

摘要

胃癌（GC）具有高度异质性，并受衰老相关因素的影响。本研究旨在通过识别与衰老相关的基因和亚型来改善胃癌的个体化预后评估。利用ESTIMATE计算了GEO和TCGA数据库中GC样本的免疫评分，并将其分为高免疫（IS_high）和低免疫（IS_low）。采用单变量 Cox 回归确定预后相关基因。LASSO 回归分析用于构建预后模型。应用 GSVA 富集分析确定通路。CCK-8、伤口愈合和Transwell试验检测了GC细胞系（AGS）的增殖、迁移和侵袭。使用流式细胞术、β-半乳糖苷酶染色法和 Western 印迹法检测了细胞周期和衰老。结果发现了两种与衰老相关的 GC 亚型。亚型2的特点是存活率较低，风险较高，肿瘤微环境的免疫反应较强。从衰老相关基因中筛选出的三个基因（IGFBP5、BCL11B和AKR1B1）被用来建立预后模型。该模型的AUC值大于0.669，显示出很强的预后价值。体外研究发现，IGFBP5 在 AGS 细胞中的过表达会降低活力、迁移和侵袭，改变细胞周期，增加衰老生物标志物（SA-β-半乳糖苷酶、p53 和 p21）。这项分析揭示了 GC 两个亚型的免疫特征以及与衰老相关的预后基因。为三个衰老相关基因（IGFBP5、BCL11B 和 AKR1B1）建立的预后模型显示出良好的预后性能，为针对 GC 的个性化治疗策略奠定了基础。

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Gastric Cancer Immune Subtypes and Prognostic Modeling: Insights from Aging-Related Gene Analysis

Gastric cancer (GC) is highly heterogeneous and influenced by aging-related factors. This study aimed to improve individualized prognostic assessment of GC by identifying aging-related genes and subtypes. Immune scores of GC samples from GEO and TCGA databases were calculated using ESTIMATE and scored as high immune (IS_high) and low immune (IS_low). ssGSEA was used to analyze immune cell infiltration. Univariate Cox regression was employed to identify prognosis-related genes. LASSO regression analysis was used to construct a prognostic model. GSVA enrichment analysis was applied to determine pathways. CCK-8, wound healing, and Transwell assays tested the proliferation, migration, and invasion of the GC cell line (AGS). Cell cycle and aging were examined using flow cytometry, β-galactosidase staining, and Western blotting. Two aging-related GC subtypes were identified. Subtype 2 was characterized as lower survival probability and higher risk, along with a more immune-responsive tumor microenvironment. Three genes (IGFBP5, BCL11B, and AKR1B1) screened from aging-related genes were used to establish a prognosis model. The AUC values of the model were greater than 0.669, exhibiting strong prognostic value. In vitro, IGFBP5 overexpression in AGS cells was found to decrease viability, migration, and invasion, alter the cell cycle, and increase aging biomarkers (SA-β-galactosidase, p53, and p21). This analysis uncovered the immune characteristics of two subtypes and aging-related prognosis genes in GC. The prognostic model established for three aging-related genes (IGFBP5, BCL11B, and AKR1B1) demonstrated good prognosis performance, providing a foundation for personalized treatment strategies aimed at GC.

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来源期刊

Critical Reviews in Immunology 医学-免疫学

CiteScore

2.60

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Immunology covers a broad spectrum of investigations at the genes, molecular, cellular, organ and system levels to reveal defense mechanisms against pathogens as well as protection against tumors and autoimmune diseases. The great advances in immunology in recent years make this field one of the most dynamic and rapidly growing in medical sciences. Critical ReviewsTM in Immunology (CRI) seeks to present a balanced overview of contemporary adaptive and innate immune responses related to autoimmunity, tumor, microbe, transplantation, neuroimmunology, immune regulation and immunotherapy from basic to translational aspects in health and disease. The articles that appear in CRI are mostly obtained by invitations to active investigators. But the journal will also consider proposals from the scientific community. Interested investigators should send their inquiries to the editor before submitting a manuscript.