# Impact of CD68, CD4, TNF-α, and COX-2 expression on disease-specific survival in Brazilian patients with OSCC

**Authors:** Sibele Nascimento de AQUINO, Lucas Lacerda de SOUZA, Hélen Kaline Farias BEZERRA, Daniel Gomes de ALVARENGA, Paulo Rogério Ferreti BONAN, Helder Domiciano Dantas MARTINS, Alan Roger SANTOS-SILVA, Márcio Ajudarte LOPES, Pablo Agustin VARGAS

PMC · DOI: 10.1590/1807-3107bor-2025.vol39.121 · 2025-11-17

## TL;DR

This study examines how the expression of four inflammatory markers affects survival in Brazilian patients with oral cancer.

## Contribution

The study identifies COX-2 as a predictor of poor survival in oral squamous cell carcinoma.

## Key findings

- High COX-2 expression correlates with larger tumor size and shorter survival in OSCC.
- High TNF-α expression is more common in moderately/poorly differentiated OSCC.
- Surgery without adjuvant therapy increases the risk of death in OSCC patients.

## Abstract

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck. Studies on the inflammatory pathways that have evolved during the development of the disease remain controversial. We assessed the expression of inflammatory markers, such as COX (cyclooxygenase)-2, CD68, CD4, and tumor necrosis factor (TNF)-α, based on prognostic variables and disease-specific survival in patients with OSCC. Immunohistochemical analysis of COX-2, TNF-α, CD4, and CD68 was conducted in 72 patients treated surgically. Neural invasion was evaluated based on S100 expression. Disease-specific survival was assessed using Cox regression analysis. Most participants were male, with a mean age of 61 years. A total of 77.5% of patients presented with clinical stages III–IV, and 70% underwent surgery combined with radiotherapy or chemotherapy. The expression of CD68, CD4, and TNF-α was not associated with clinical variables or tumor differentiation. COX-2 expression correlated with tumor size (p = 0.01), whereas high TNF-α expression was noted in moderately/poorly differentiated OSCC. The absence of nodal involvement (hazard ratio [HR]: 0.47, confidence interval [CI]: 0.25–0.87, p = 0.001) was linked to lower death risk, whereas surgery without adjuvant radiotherapy or chemotherapy was associated with a higher risk of death (HR: 2.09, 95%CI: 1.02–4.27, p = 0.043). Multivariate analysis revealed that high COX-2 expression predicted a shorter disease-specific survival. Altogether, high TNF-α expression is prevalent in moderately/poorly differentiated OSCC, and elevated COX-2 expression correlates with larger tumor size and poorer survival in OSCC.

## Linked entities

- **Genes:** CD68 (CD68 molecule) [NCBI Gene 968], CD4 (CD4 molecule) [NCBI Gene 920], TNF (tumor necrosis factor) [NCBI Gene 7124], COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513], S100A1 (S100 calcium binding protein A1) [NCBI Gene 6271]
- **Diseases:** oral squamous cell carcinoma (MONDO:0004958)

## Full-text entities

- **Genes:** COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CD68 (CD68 molecule) [NCBI Gene 968] {aka GP110, LAMP4, SCARD1}, S100A1 (S100 calcium binding protein A1) [NCBI Gene 6271] {aka S100, S100-alpha, S100A}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** malignancy (MESH:D009369), death (MESH:D003643), nodal (MESH:D013611), inflammatory (MESH:D007249), and neck (MESH:D006258), OSCC (MESH:D000077195)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12628726/full.md

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Source: https://tomesphere.com/paper/PMC12628726