Interleukin-1 receptor antagonist (IL1RN) is associated with suppression of early carcinogenic events in human oral malignancies

Abstract

Inflammatory abnormalities have been implicated in the pathogenesis of various human diseases, including cancer. Interleukin-1 receptor antagonist (IL1RN) is a potent anti-inflammatory molecule that modulates the biological activity of the proinflammatory cytokine, interleukin-1. The aim of this study was to examine the expression of IL1RN in oral squamous cell carcinomas (OSCCs), and to determine its clinical significance. Expression levels of IL1RN in matched normal and tumor specimens from 39 OSCCs were evaluated using real-time quantitative polymerase chain reaction methods, and immunohistochemical analysis. Protein expression of IL1RN was also examined in 18 oral premalignant lesions (OPLs). Expression of IL1RN mRNA was significantly downregulated in OSCCs compared with normal tissues. Decreased expression of IL1RN protein was also observed in OPLs and OSCCs. The IL1RN expression level was lower in the OPL cases with severe dysplasia compared to those with mild/moderate dysplasia. Significantly downregulated IL1RN expression was observed in all OSCC lesion sites examined when compared with the matched normal tissues. However, the decreased level of IL1RN expression did not correspond with tumor progression. Noteworthy, IL1RN expression was higher in the advanced OSCC cases (T3/T4) compared to early cases (T1/T2). Among OSCC samples, relatively higher IL1RN expression was associated with active tumor development in the OSCCs occurring in the buccal mucosa, oral floor, fauces and gingiva, but not the tongue. These data suggest that IL1RN may exhibit opposing characteristics in oral malignancies depending on the stage of cancer development, suppressing early carcinogenic events, yet promoting tumor development in some lesion sites. Thus, IL1RN could represent a reliable biomarker for the early diagnosis of OSCCs. Furthermore, IL1RN may possess unknown and complex functions in the developed OSCC.

Discovery and preclinical validation of proteomic biomarkers in saliva for early detection of oral squamous cell carcinomas

“…IL1RN could reduce tumor growth and invasiveness by suppressing IL‐1‐related activities. Previous studies indicated that IL1RN expression was significantly reduced in OSCC tissues as assessed by quantitative real‐time PCR and immunohistochemistry (Lallemant et al, ; Shiiba et al, ). Consistent with these clinical observations, our findings suggested that IL1RN expression was also downregulated in the saliva of OSCC patients.…”

“…Then, solute carrier family 3 member 2 (SLC3A2), S100 calcium‐binding protein A2 (S100A2), and interleukin‐1 receptor antagonist protein (IL1RN) were selected and further prevalidated using enzyme‐linked immunosorbent assay (ELISA) in the three groups. Previous studies have reported the abnormal expression of these three proteins in OSCC tissue samples (Kumar et al, ; Shiiba et al, ; Toyoda et al, ). However, those studies were not based on biomarker detection from saliva samples.…”

<b><i>IL1RN</i></b> Polymorphisms Are Associated with a Decreased Risk of Esophageal Cancer Susceptibility in a Chinese Population

“…We selected four candidate SNPs in the IL1RN gene from the database of SNPs and previously published polymorphisms associated with cancers [16, 19]. Each SNP had a minor allele frequency >5% in the global population from the 1000 Genomes Project (http://www.internationalgenome.org/).…”

“…IL1RN is a natural antagonist of IL-1 and modulates a variety of IL-1-related immune and inflammatory responses. So far, studies of variants in ­ IL1RN in individuals have shown that IL1RN polymorphisms are involved in an increased risk of pulmonary tuberculosis [15], oral malignancy [16], and gastric cancer [14]. Researchers also reported that IL1RN variants are associated with the risk of breast cancer in the female population of South Korea, India, and China [17-19].…”

Analysis of the expression and potential molecular mechanism of interleukin-1 receptor antagonist (IL1RN) in papillary thyroid cancer via bioinformatics methods

“…The balance between IL1RN and IL-1 plays a crucial role in many diseases, including cancer [10]. IL1RN has been studied in several cancers, including prostate carcinoma [11][12], cervical carcinoma [13], gastric carcinoma [14], bronchogenic carcinoma [15], endometrial cancer [16], lung cancer [17], ovarian cancer [18], oral malignancies [19], leukemia [20], and other cancers.…”