Abstract
Thyroid hormone levels may be associated with disease outcome in head and neck squamous cell carcinoma (HNSCC). µ-Crystallin (CRYM), a thyroid hormone binding protein, blocks intracellular binding of the thyroid hormone T3 to its receptors. In this study, we aimed to analyze the association of CRYM levels with disease outcome in HNSCC patients. We retrospectively assessed immunohistochemical CRYM expression in 121 head and neck cancer patients. Preoperative thyrotropin levels could be extracted for 50 patients. Patients with low thyrotropin levels had a worse prognosis compared to euthyroid patients (5-year overall survival TSH low 20% vs. TSH norm 58%). We observed an association of CRYM+ patients with improved overall survival (5-year overall survival for CRYM+ 78.6% vs. CRYM− 56%). Interaction analysis between CRYM and HPV revealed that this effect was limited to HPV− patients (CRYM+|HPV− HR 0.12, 95% CI 0.01–0.87, p = 0.036). These results were replicated in an independent dataset. CRYM expression identified patients with favorable disease progression for HPV− HNSCC patients and could serve as a useful biomarker in this patient population. This study further confirms a correlation of thyroid hormone levels with adverse disease outcome in HNSCC patients, which could be potentially exploited as a therapeutic target.
Highlights
Head and neck cancer is listed among the ten most frequently diagnosed malignant diseases with an estimated incidence rate of 700,000 cases and 360,000 deaths per year worldwide [1]
One protein that interferes with the thyroid hormone pathway is μ-crystallin (CRYM)
Univariable Cox models showed statistically significant differences for overall survival (CRYM high Hazard ratios (HR): 0.08; 95% CI: 0.01–0.54, p = 0.002) and DFS
Summary
Head and neck cancer is listed among the ten most frequently diagnosed malignant diseases with an estimated incidence rate of 700,000 cases and 360,000 deaths per year worldwide [1]. The vast majority of head and neck cancers are squamous cell carcinoma (HNSCC) [2]. Survival rates of this cancer entity remain poor and patients are often confronted with disease recurrence despite advances in diagnostic tools and therapeutic possibilities [2]. In HNSCC, Nelson et al were able to observe an association between patients who developed hypothyroidism after radiation therapy and improved survival in 155 patients [8] These results could be subsequently verified by a SEER database analysis of nearly 6000 patients [9]. One protein that interferes with the thyroid hormone pathway is μ-crystallin (CRYM) This protein has the capability of NADPH-dependent binding of T3 within the cytoplasm and suppressing T3-mediated gene expression [11,12]. We aimed to investigate the impact of thyroid hormones and CRYM in a HNSCC cohort
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