Epiregulin: A new prognostic molecule in non-Hodgkin lymphoma.

BACKGROUND: Epiregulin is a molecule that plays a role in cell proliferation, tumor development, inflammation, and angiogenesis in malignant diseases. AIM: Our study aims to reveal, for the first time, the predictive value of this molecule in non-Hodgkin lymphoma (NHL) and its association with disease stage, cell type, and extranodal involvement. METHODS: The study is an observational case-control trial involving 60 newly diagnosed NHL patients and 60 healthy individuals (control group) between 18 and 75 years old. Demographic characteristics of all volunteers, stages of patients' illnesses and lymphoma cell types, hemogram, biochemistry tests, beta 2-microglobulin, C-reactive protein (CRP), and epiregulin levels were measured and statistically evaluated. RESULTS: Epiregulin levels were significantly higher in NHL patients compared to the control group (P < 0.0001). Similarly, a significant increase in epiregulin levels was observed in advanced NHL patients. Furthermore, the most common NHL subgroup within the NHL group, diffuse Large B Cell Lymphoma (DLBCL), and the subgroup with extranodal involvement also had significantly higher levels of epiregulin. A positive correlation was found between the epiregulin molecule and CRP, beta 2-microglobulin, and lactate dehydrogenase (LDH) levels in NHL patients. CONCLUSION: Our study suggests that serum epiregulin levels, discovered to increase in NHL patients for the first time, may be an independent predictive molecule in an advanced stage, extranodal involvement, and the DLBCL subtype of this disease. Epiregulin positively correlates with prognostic molecules such as beta 2-microglobulin, LDH, and CRP. Illuminating its potential role in NHL pathogenesis could make epiregulin a vital drug target for treatment.

MiR-192-5p suppresses M1 macrophage polarization via epiregulin (EREG) downregulation in gouty arthritis.

Gouty arthritis (GA) is a chronic inflammatory disease characterized by the deposition of monosodium urate (MSU) crystals within joints. MiR-192-5p is shown to be low-expressed in GA patients. However, the potential mechanism involving miR-192-5p in GA remains unclear. In the current study, a significant reduction in miR-192-5p and an increase in epiregulin (EREG) were observed in serum of GA patients, suggesting that miR-192-5p and EREG were involved in the pathogenic process of GA. A mouse GA model was established via 0.5 mg/20 µL MSU crystal administration. To investigate the effect of miR-192-5p on GA, mice were injected with miR-192-5p agomir or NC agomir before modeling. We found that miR-192-5p overexpression induced by miR-192-5p agomir reduced EREG expression, attenuated ankle joint swelling and synovial inflammatory cell infiltration and improved bone erosion in MSU-induced GA mice. MiR-192-5p decreased CD16/32+ (M1 marker) macrophages, but increased CD206 (M2 marker) expression in synovium of GA models. In vitro, RAW264.7 macrophages were stimulated with miR-192-5p mimic or NC mimic under IFNγ plus LPS-stimulated M1 polarization condition. MiR-192-5p reduced the release of inflammatory cytokines TNF-α and IL-1ß, decreased iNOS expression, and inhibited CD16/32 expression, indicating the blockade of M1 macrophage activation. Luciferase reporter system revealed the target interaction between miR-192-5p and EREG. Further rescue experiments demonstrated that EREG overexpression partly reversed the inhibitory role of miR-192-5p on M1 macrophage polarization manifested by elevated iNOS and CD16/32 levels. Collectively, miR-192-5p ameliorates inflammatory response in GA by inhibiting M1 macrophage activation via inhibiting EREG protein.

Polymorphism in the EREG gene confers susceptibility to tuberculosis.

BACKGROUND: Host genetic factors affect the immune response to Mycobacterium tuberculosis (Mtb) infection as well as the progression of the disease. Epiregulin (EREG) belongs to the epidermal growth factor (EGF) family, which binds to the epidermal growth factor receptor (EGFR) to regulate the immune response of the host during infections. Our study aimed to compare EREG levels in tuberculosis (TB) patients and healthy controls and assess whether polymorphisms in EREG increase the risk of TB. METHODS: We used ELISA to determine the plasma EREG level from 30 healthy controls and 50 tuberculosis patients. By evaluating the EREG gene from 624 TB patients and 600 healthy controls, we determined the allelic and genotypic frequencies for association with susceptibility to TB infections in this group. RESULTS: This paper shows that the pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) groups showed a significantly higher plasma EREG level (1014 ± 733.9 pg/ml, 700.2 ± 676.6 pg/ml, respectively) than the healthy controls (277 ± 105.4 pg/ml). The rs2367707 polymorphism was associated with a higher risk of PTB and EPTB (P = 0.00051, P = 0.0012). Analyses of haplotype frequencies found that people with the haplotype CACAT had a higher risk of PTB and EPTB (P = 0.00031, OR = 1.43; P = 0.000053, OR = 1.65). Moreover, the rs6446993 polymorphism of the EREG gene was found to be associated with EPTB (P = 0.00087, OR = 1.54; 95% CI = 1.23-1.94). CONCLUSIONS: Compared to that of healthy controls, the level of EREG in the plasma of TB patients increased significantly. Based on these data, we demonstrated that EREG polymorphisms are genetic factors for susceptibility to TB and various forms of TB.

Association between serum ligands and the skin toxicity of anti-epidermal growth factor receptor antibody in metastatic colorectal cancer.

Skin toxicity is a known clinical signature used to predict the prognosis of anti-epidermal growth factor receptor (EGFR) antibody treatment in metastatic colorectal cancer (mCRC). There are no biological markers to predict skin toxicity before anti-EGFR antibody treatment in mCRC patients. Between August 2008 and August 2011, pretreatment serum samples were obtained from KRAS wild-type (WT) patients who received anti-EGFR antibody treatment. Serum levels of ligands were measured by ELISA. A total of 103 KRAS WT patients were enrolled in the study. Progression-free survival and overall survival of patients with a high grade (grade 2-3) of skin toxicity were significantly longer than those with a low grade (grade 0-1) of skin toxicity (median progression-free survival, 6.4 months vs 2.4 months, P < 0.001; median overall survival, 14.6 months vs 7.1 months, P = 0.006). There were significant differences in distribution of serum levels of epiregulin (EREG), amphiregulin (AREG), and hepatocyte growth factor (HGF) between groups of low/high grade of skin toxicity (P < 0.048, P < 0.012, P < 0.012, respectively). In addition, serum levels of HGF, EREG, and AREG were inversely proportional to grades of skin toxicity as determined by the Cochran-Armitage test (P = 0.019, P = 0.047, P = 0.021, respectively). Our study indicated that serum levels such as HGF, EREG, and AREG may be significant markers to predict the grade of skin toxicity and the prognosis of anti-EGFR antibody treatment, which contribute to improvement of the management of skin toxicity and survival time in mCRC patients.