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CD68作为消化系统癌症的多组学预后生物标志物:与肿瘤浸润免疫细胞和免疫检查点的相关性

CD68 as a multi-omic prognostic biomarker in digestive system cancers: correlations with tumor-infiltrating immune cells and immune checkpoints.

作者信息

Li Hui, Zhang Hui, Dai Rujiang, Zheng Dian, Zhao Jianghai, Jing Hong, Ma Xuhui, Zhang Lin, Sun Weihong, Suo Zhimin

机构信息

Department of Digestion, Huaihe Hospital of Henan University, Kaifeng, China.

Department of Pathology, Huaihe Hospital of Henan University, Kaifeng, China.

出版信息

Front Immunol. 2025 Aug 21;16:1599677. doi: 10.3389/fimmu.2025.1599677. eCollection 2025.

DOI:10.3389/fimmu.2025.1599677
PMID:40918116
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12408268/
Abstract

BACKGROUND AND OBJECTIVE

CD68 plays a crucial role in promoting phagocytosis. However, its expression level, prognostic value and the correlations with tumor-infiltrating immune cells (TIICs) or common tumor immune checkpoints (TICs) in human digestive system cancers (DSC) remain poorly understood. This study aims to investigate the expression levels, prognostic significance, and clinical implications of CD68, as well as its correlations with six TIICs and four common TICs in DSC.

MATERIALS AND METHODS

We analyzed CD68 mRNA and protein expression using online databases and immunohistochemistry (IHC) on tissue microarray (TMA) sections, comparing DSC tumor tissues with adjacent normal tissues. Overall survival (OS) was calculated to evaluate the prognostic value of CD68 in DSC. Additionally, correlations between CD68 expression and six TIICs (B cells, CD4+ T cells, CD8+ T cells, macrophages, NK cells, and cancer-associated fibroblasts) or four common TICs (PDCD1, CTLA4, IDO1, and CD40) were assessed using the Tumor Immune Estimation Resource (TIMER).

RESULTS

CD68 mRNA expression was significantly higher in esophageal carcinoma (ESCA) and stomach adenocarcinoma (STAD) tissues compared to adjacent normal tissues, but lower in colon adenocarcinoma (COAD), liver hepatocellular carcinoma (LIHC), and pancreas invasive ductal carcinoma (PAAD). Protein expression of CD68 was significantly higher in COAD than in adjacent normal tissues, but lower in ESCA, LIHC, PAAD, and STAD. CD68 protein expression served as a prognostic marker in COAD and STAD. Furthermore, CD68 expression showed strong positive correlations with the six TIICs and significant positive correlations with the four TICs in DSC.

CONCLUSION

CD68 may serve as an essential prognostic biomarker in COAD and STAD and could be a promising candidate for diagnostic, prognostic, and therapeutic targeting in human DSC.

摘要

背景与目的

CD68在促进吞噬作用中起关键作用。然而,在人类消化系统癌症(DSC)中,其表达水平、预后价值以及与肿瘤浸润免疫细胞(TIICs)或常见肿瘤免疫检查点(TICs)的相关性仍知之甚少。本研究旨在探讨CD68在DSC中的表达水平、预后意义及临床意义,以及它与六种TIICs和四种常见TICs的相关性。

材料与方法

我们使用在线数据库和组织微阵列(TMA)切片上的免疫组织化学(IHC)分析CD68 mRNA和蛋白表达,将DSC肿瘤组织与相邻正常组织进行比较。计算总生存期(OS)以评估CD68在DSC中的预后价值。此外,使用肿瘤免疫评估资源(TIMER)评估CD68表达与六种TIICs(B细胞、CD4+ T细胞、CD8+ T细胞、巨噬细胞、NK细胞和癌症相关成纤维细胞)或四种常见TICs(PDCD1、CTLA4、IDO1和CD40)之间的相关性。

结果

与相邻正常组织相比,食管癌(ESCA)和胃腺癌(STAD)组织中CD68 mRNA表达显著更高,但在结肠腺癌(COAD)、肝细胞癌(LIHC)和胰腺浸润性导管癌(PAAD)中较低。COAD中CD68蛋白表达显著高于相邻正常组织,但在ESCA、LIHC、PAAD和STAD中较低。CD68蛋白表达在COAD和STAD中作为预后标志物。此外,在DSC中,CD68表达与六种TIICs呈强正相关,与四种TICs呈显著正相关。

结论

CD68可能是COAD和STAD中一种重要的预后生物标志物,并且可能是人类DSC诊断、预后和治疗靶向的有前景的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fa/12408268/7d67f0dc5eb7/fimmu-16-1599677-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fa/12408268/807bcddb55f1/fimmu-16-1599677-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fa/12408268/d44c1e1776c0/fimmu-16-1599677-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fa/12408268/06a60a853322/fimmu-16-1599677-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fa/12408268/4ad4a429a1c4/fimmu-16-1599677-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fa/12408268/e09c758b8693/fimmu-16-1599677-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fa/12408268/7d67f0dc5eb7/fimmu-16-1599677-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fa/12408268/807bcddb55f1/fimmu-16-1599677-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fa/12408268/d44c1e1776c0/fimmu-16-1599677-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fa/12408268/06a60a853322/fimmu-16-1599677-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fa/12408268/4ad4a429a1c4/fimmu-16-1599677-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fa/12408268/e09c758b8693/fimmu-16-1599677-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fa/12408268/7d67f0dc5eb7/fimmu-16-1599677-g006.jpg

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