Expression of IL-1α correlates with distant metastasis in patients with head and neck squamous cell carcinoma

Abstract

The presence of IL-1 in human cancers is associated with aggressive tumor biology but its prognostic value is unknown. We studied whether IL-1α expression is a prognostic marker of distant metastasis in patients with head and neck squamous cell carcinoma (HNSCC). IL-1α mRNA and protein levels were determined in tumor samples and cancer cell lines using RT-PCR and ELISA. The effects of constitutive IL-1α expression by tumor lines were characterized. IL-1α mRNA and protein secretion were higher in tumor samples from patients who later developed distant metastasis than in patients who did not. By using distant metastasis as a dependent variable, patients were classified into two categories of IL-1α transcript-levels. The high-IL-1α group had a significantly lower five-year distant metastasis-free survival than the low-IL-1α group [70.0% (CI 95%: 55.9-84.1%) vs 94.7% (CI 95%:90.2-99.2%)]. When IL-1α transcript-levels were combined with clinical factors related to tumor metastasis, the predictive power of the model increased significantly. Additionally, transcript levels of IL-1α correlated significantly with those of the IL-1 family genes and genes related to the metastatic process. IL-1 treatment of microvascular endothelial cells increased adhesion of HNSCC cells but no differences were found based on constitutive IL-1α expression by tumor cells. Nevertheless, IL-1α produced by tumor cells effectively increased their transmigration across the endothelium. We found a significant relationship between IL-1α expression and development of distant metastasis in HNSCC patients. IL-1α expression could help to define a subset of patients at high risk of distant metastasis who could benefit from adjuvant treatment.

Interleukin 1α and the inflammatory process

“…IL-1α mRNA and protein expression were found to be higher in tumor samples from patients who later developed distant metastases than in tumors from patients who did not. Patients who had high IL-1α expression in tumors had significantly lower 5-year survival rates than patients with low IL-1α expression 101 . Analysis of genetic risk factors for the development of ovarian cancer in a large patient cohort (15,604 cases) showed a significant association between the Il1a single nucleotide polymorphism (SNP) rs17561 and reduced susceptibility to clear cell ovarian cancer type.…”

“…Confirmation of the critical contribution of IL-1α to tumor development in humans comes from the field of clinical oncology. In patients with head and neck squamous cell carcinoma, IL-1α expression has been evaluated as a prognostic marker of distant metastases 101 . IL-1α mRNA and protein expression were found to be higher in tumor samples from patients who later developed distant metastases than in tumors from patients who did not.…”

Function and regulation of IL‐1α in inflammatory diseases and cancer

“…Furthermore, both IL‐1β and VEGF synergize to promote angiogenesis in the tumors . Increased IL‐1α production is associated with distant metastases, and poor survival rate in head and neck squamous cell carcinoma and gastric carcinoma . IL‐1α is also a major driver of colon cancer that is associated with chronic inflammation in the colon .…”

“…203 Increased IL-1α production is associated with distant metastases, and poor survival rate in head and neck squamous cell carcinoma and gastric carcinoma. 204,205 IL-1α…”

Role of Inflammatory Markers in Prognosis of Oral Squamous Cell Carcinoma

“…However, this inflammatory microenvironment leads to macrophage migration and production of oxygen-reactive species, leading to metastasis in lymph nodes (León et al, 2015). TNF-α autocrine activation is associated with tumour growth (Landskron et al, 2014) through mechanisms such as increased cell proliferation that are dependent on NF-κB activation (Tang et al, 2017); reduction of apoptosis and inactivation tumour suppressor genes (Zhang et al, 2014); increased synthesis of matrix metalloproteinases, which is closely related to the local invasion and the distance of malignant cells (Tang et al, 2017); induction of metastasis and angiogenesis (Zhou et al, 2015); and increased expression in endothelial cells of proteins that mediate the adhesion of VCAM-1 (Song et al, 2012).…”