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Original Investigation |

Serum Biomarkers in Head and Neck Squamous Cell Cancer

Nadine M. Kaskas, BS1; Tara Moore-Medlin, BS2; Gloria B. McClure, MS3; Oleksandr Ekshyyan, PhD2,4; John A. Vanchiere, PhD, MD3; Cherie-Ann O. Nathan, MD2,4
[+] Author Affiliations
1Louisiana State University Health Shreveport School of Medicine, Shreveport
2Department of Otolaryngology–Head and Neck Surgery, Louisiana State University Health, Shreveport
3Department of Pediatrics, Louisiana State University Health, Shreveport
4Feist-Weiller Cancer Center, Louisiana State University Health, Shreveport
JAMA Otolaryngol Head Neck Surg. 2014;140(1):5-11. doi:10.1001/jamaoto.2013.5688.
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Published online

Importance  Serum biomarkers may be useful in the evaluation of suspected head and neck squamous cell cancer (HNSCC) and as indicators of treatment success or failure in adjuvant and chemopreventive clinical trials.

Objective  To determine serum cytokine and chemokine concentrations altered in patients with HNSCC compared with healthy volunteers to identify potential biomarkers.

Design, Setting, and Participants  A retrospective experimental laboratory study at Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport. Serum samples from 50 patients with stages II, III, and IV HNSCC and 20 healthy volunteers were available for study. Primary tumor sites represented in the patient group included the nasal cavity, oral cavity, oropharynx, hypopharynx, and larynx.

Interventions  Following institutional review approval and written informed consent, blood samples were drawn from patients. No intervention, to include any kind of diagnostic workup or treatment, was provided to patients during the course of this study.

Main Outcomes and Measures  The main outcome measures were the quantification of cytokine and chemokine concentrations in serum samples. Luminex multiplex panel technology was used for simultaneous measurement of 18 analytes, including fibroblast growth factor 2, granulocyte-macrophage colony-stimulating factor, growth-related oncogene, interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, inducible protein (IP)-10, soluble CD40 ligand, tumor necrosis factor, and vascular endothelial growth factor.

Results  The serum samples of patients with HNSCC contained lower levels of IFN-γ (mean patient serum level, 6.08 pg/mL, compared with the mean control level, 26.20 pg/mL; P = .004), IL-13 (mean patient serum level, 2.85 pg/mL, compared with the control mean level, 7.23 pg/mL; P = .02), and macrophage inflammatory protein-1β (MIP-1β) (mean patient serum level, 14.91 pg/mL, compared with the mean control level, 28.98 pg/mL; P = .004), and elevated levels of IP-10 (mean patient serum level, 359.24 pg/mL, compared with mean control level, 216.40 pg/mL; P = .04). All other markers tested were not significantly different between patients with cancer and controls.

Conclusions and Relevance  This pilot study demonstrated a significant decrease in serum IFN-γ, IL-13, and MIP-1β levels and a significant elevation of serum IP-10 concentration in patients with HNSCC, irrespective of primary tumor site. If validated in larger, independent studies, these serum biomarkers may be useful in the diagnosis and treatment of HNSCC. In the future, a defined, multianalyte screening panel could facilitate early diagnosis of HNSCC, allowing for earlier treatment and thereby reducing patient mortality.

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Figures

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Figure 1.
Interferon-γ (IFN-γ) Serum Concentration

Serum samples of patients with head and neck squamous cell carcinoma (HNSCC) contained lower levels of IFN-γ (mean level, 6.08 pg/mL) compared with those of controls (mean level, 26.20 pg/mL) (P = .004). Error bars indicate standard error.

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Figure 2.
Interleukin (IL)-13 Serum Concentration

Serum samples of patients with head and neck squamous cell carcinoma (HNSCC) contained lower levels of IL-13 (mean level, 2.85 pg/mL) compared with those of controls (mean level, 7.23 pg/mL) (P = .02). Error bars indicate standard error.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Macrophage Inflammatory Protein (MIP)-1β Serum Concentration

Serum samples of patients with head and neck squamous cell carcinoma (HNSCC) contained lower levels of MIP-1β (mean level, 14.91 pg/mL) compared with those of controls (mean level, 28.98 pg/mL) (P = .004). Error bars indicate standard error.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.
Inducible Protein (IP)-10 Serum Concentration

Serum samples of patients with head and neck squamous cell carcinoma (HNSCC) contained elevated levels of IP-10 (mean level, 359.24 pg/mL) compared with those of controls (mean level, 216.40 pg/mL) (P = .04). Error bars indicate standard error.

Graphic Jump Location

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