ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1599677
CD68 as a Multi-Omic Prognostic Biomarker in Digestive System Cancers: Correlations with Tumor-Infiltrating Immune Cells and Immune Checkpoints
Provisionally accepted
- Henan University, Kaifeng, China
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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.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.
Keywords: CD68, Digestive system cancers, macrophage, prognosis, biomarker, Immune checkpoint
Received: 25 Mar 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Suo, Li, Zhang, Dai, Zheng, Zhao and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhimin Suo, Henan University, Kaifeng, China
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