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ITGAL 作为与胃癌免疫浸润相关的预后生物标志物

英文原题:ITGAL as a Prognostic Biomarker Correlated With Immune Infiltrates in Gastric Cancer.

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ITGAL as a Prognostic Biomarker Correlated With Immune Infiltrates in Gastric Cancer.

PubMed 2022/03/24(内容时间) Front Cell Dev Biol Q1 · IF 5.3(JCR 2025)

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中文摘要

整合素αL(ITGAL)是整合素家族的一员,其异常表达与癌变和免疫调节有关。然而,ITGAL与胃癌(GC)预后及TIL(肿瘤浸润淋巴细胞)(TILs)之间的关系尚不明确。通过Gene Expression Profiling Interaction Analysis(GEPIA)、UALCAN、Tumor Immune Estimation Resource(TIMER)和Kaplan-Meier(KM)plotter等多个数据库,系统分析了ITGAL在人类肿瘤中的差异表达及在GC中的临床预后。使用TIMER、GEPIA和TISIDB数据库全面研究了ITGAL与肿瘤浸润免疫细胞的相关性。

此外,通过免疫组织化学、qRT-PCR和Western blot进一步研究了结果。我们发现GC样本中ITGAL表达显著高于瘤周样本。样本类型、亚组、癌症分期、淋巴结分期和较差的生存率与ITGAL高表达密切相关。

此外,ITGAL表达上调与胃腺癌(STAD)中的免疫调节因子、趋化因子以及CD8+、CD4+ T细胞、B细胞、单核细胞、中性粒细胞、巨噬细胞、T细胞调节性细胞、NK细胞和髓系树突状细胞的浸润水平密切相关。

具体而言,免疫组织化学和生物信息学分析显示,ITGAL表达与多种免疫标志物集(包括PD1(T细胞耗竭标志物))有很强的关联。

总之,ITGAL是GC患者的预后生物标志物。它可能调节肿瘤免疫微环境导致不良预后。此外,有必要开展研究探索靶向ITGAL的治疗方法。

展开英文摘要原文

Integrin alpha L (ITGAL) is a member of the integrin family in which the abnormal expression is linked with carcinogenesis and immune regulation.

However, the relation between ITGAL and the prognosis of gastric cancer (GC) and tumor-infiltrating lymphocytes (TILs) are not well understood. The differential expressions of ITGAL in human tumors and the clinical prognosis in GC were systematically analyzed via multiple databases including Gene Expression Profiling Interaction Analysis (GEPIA), UALCAN, Tumor Immune Estimation Resource (TIMER), and Kaplan-Meier (KM) plotter.

TIMER, GEPIA, and TISIDB databases were used to comprehensively investigate the correlation between ITGAL and tumor infiltration immune cells. Also, further results were investigated by immunohistochemistry, qRT-PCR, and Western blot.

We found that ITGAL expression in GC samples was considerably increased than in peritumor samples. Sample type, subgroup, cancer stage, lymphatic node stage, and worse survival were strongly related to high ITGAL expression.

Moreover, upregulated ITGAL expression was strongly connected with immunomodulators, chemokines, and infiltrating levels of CD8 + , CD4 + T cell, B cell, monocyte, neutrophil, macrophage, T-cell regulatory, NK cell, and myeloid dendritic cell in stomach adenocarcinoma (STAD). Specifically, immunohistochemistry and bioinformatic analysis showed that ITGAL expression was shown to have strong relationships with various immunological marker sets including PD1 (T-cell exhaustion marker).

In conclusion, ITGAL is a prognostic biomarker for GC patients. It might regulate tumor immune microenvironment leading to poor prognosis.

Furthermore, studies are essential to explore therapeutic targeting ITGAL.

论文信息

作者
Zhang J、Wang H、Yuan C、Wu J、Xu J、Chen S、Zhang C、He Y
单位
Department of Center for Digestive Disease, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.China
期刊
Frontiers in cell and developmental biology2022
原文标识
PubMed 35399517 · DOI 10.3389/fcell.2022.808212