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趋化因子配体 14 与胃癌微环境中免疫细胞浸润相关并预测不良预后

英文原题:Chemokine ligand 14 correlates with immune cell infiltration in the gastric cancer microenvironment in predicting unfavorable prognosis.

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Chemokine ligand 14 correlates with immune cell infiltration in the gastric cancer microenvironment in predicting unfavorable prognosis.

PubMed 2024/06/03(内容时间) Front Pharmacol Q1 · IF 5.4(JCR 2025)

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研究概要

我们的研究表明,CCL14 是胃癌的一种不良预后生物标志物,这可能与免疫治疗的潜力有关。

研究思路结论见上方概要

胃癌(GC)是全球第三大癌症相关死亡原因;就缺乏可靠的早期诊断和免疫治疗反应预测生物标志物而言,GC患者的预后仍然很差。在此,我们旨在发现胃肿瘤微环境(TME)中趋化因子配体14(CCL14)表达与其临床意义之间的联系,并研究其与免疫细胞浸润的相关性。

我们通过生物信息学分析评估了胃癌中CCL14 mRNA表达及其与肿瘤浸润免疫细胞(TILs)的相互关系。通过多重免疫组化分析在胃癌组织芯片中检测了CCL14蛋白表达、TILs和免疫检查点。然后,我们进行统计分析以确定CCL14相关的患者生存与免疫细胞浸润之间的关联(p < 0.05)。

我们发现CCL14蛋白分别表达于胃癌组织中的癌细胞和TILs。CCL14蛋白与肿瘤分化和肿瘤浸润深度相关,并与胃癌细胞中LAG3和PD-L1的表达呈正相关。此外,胃癌组织TILs中的CCL14蛋白与Lauren分型细胞、TME中的T细胞(CD4+和CD8+)及CD68+巨噬细胞相关。Kaplan-Meier生存分析和多因素分析显示,胃癌细胞中CCL14的表达是独立预后因素。

展开英文摘要原文

Gastric cancer (GC) is the world's third-leading cause of cancer-related mortality; the prognosis for GC patients remains poor in terms of a lack of reliable biomarkers for early diagnosis and immune therapy response prediction. Here, we aim to discover the connection between chemokine ligand 14 (CCL14) expression in the gastric tumor microenvironment (TME) and its clinical significance and investigate its correlation with immune cell infiltration.

We assessed CCL14 mRNA expression and its interrelation with tumor-infiltrating immune cells (TILs) using bioinformatics analysis in gastric cancer. CCL14 protein expression, TILs, and immune checkpoints were detected by multiple immunohistochemistry analyses in gastric cancer tissue microarrays. Then, we conducted statistics analysis to determine the association between CCL14-related patient survival and immune cell infiltration ( p < 0.05).

We found that the CCL14 protein was separately expressed in the carcinoma cells and TILs in stomach cancer tissues. The CCL14 protein was related to tumor differentiation and tumor depth and positively correlated with the presentation of LAG3 and PD-L1 in gastric cancer cells. In addition, the CCL14 protein in the TILs of gastric cancer tissues was related to Lauren's type cells, T cells (CD4 + and CD8 + ), and CD68 + macrophages in the TME. Kaplan-Meier survival and multivariate analyses showed that the CCL14 expression in gastric cancer cells was an independent prognostic factor.

Our study illustrated that CCL14 is a poor prognosis biomarker in gastric cancer, which may be associated with the potential for immunotherapy.

论文信息

作者
Lu B、Shi J、Cheng T、Wang C、Xu M、Sun P、Zhang X、Yang L
第一作者单位
Department of Clinical Biobank, Nantong University Affiliated Hospital, Nantong, China.China
通讯作者单位
Department of Gastroenterology, Nantong University Affiliated Hospital, Nantong, Jiangsu, China.China
期刊
Frontiers in pharmacology2024
原文标识
PubMed 38887558 · DOI 10.3389/fphar.2024.1397656