sRAGE downregulates the VEGF expression in OHSS ovarian granulosa cells.

OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is mainly caused by human chorionic gonadotropin (hCG) through vasoactive mediators such as vascular endothelial growth factor (VEGF) and various inflammatory factors. Our previous study showed that soluble receptor for advanced glycation end products (sRAGE) played a protective role in PCOS by inhibiting VEGF, so wanted to explore the role of sRAGE in OHSS. METHODS: Two sets of experiments were performed in this study. In part one, sRAGE protein levels in follicular fluid (FF) samples from 60 patients with OHSS and 60 non-OHSS patients were measured by ELISA. In part two, ovarian granulosa cells were isolated from an additional 25 patients with OHSS and cultured. Then, ovarian granulosa cells were treated with different concentrations of sRAGE. Granulosa cells cultured without sRAGE stimulation were used as the control group. The levels of VEGF, amphiregulin (AREG), betacellulin (BTC), and epiregulin (EREG) mRNA were examined by quantitative RT-PCR. The protein levels of VEGF, AREG, BTC, and EREG were measured by ELISA. RESULTS: Compared with non-OHSS patients, patients with OHSS exhibited lower sRAGE levels in both serum and FF (p < .05). Treatment with sRAGE decreased the production of VEGF, and the effects were dependent on the concentration of sRAGE (p < .05). Simultaneously, the expression of the EGF-like growth factors AREG, BTC and EREG was decreased, and their expression was dependent on the concentration of sRAGE (p < .05). CONCLUSIONS: sRAGE downregulate VEGF expression in OHSS ovarian granulosa cells, in which EGF-like growth factor pathway may be involved, and sRAGE may play a potential protective role in OHSS.

Model establishment of prognostic-related immune genes in laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck in the world. At present, the treatment methods include surgery, radiotherapy, and chemotherapy, but the 5-year survival rate is still not ideal and the quality of life of the patients is low. Due to the relative lack of immunotherapy methods, this study aims to build a risk prediction model of related immune genes, which can be used to effectively predict the prognosis of laryngeal cancer patients, and provide targets for subsequent immunotherapy. METHODS: We collected the 111 cases of laryngeal squamous cell carcinoma and 12 matched normal samples in the The Cancer Genome Atlas Database (TCGA) gene expression quantification database. The differentially expressed related immune genes were screened by R software version 3.5.2. The COX regression model of immune related genes was constructed, and the sensitivity and specificity of the model were evaluated. The risk value was calculated according to the model, and the risk curve was drawn to verify the correlation between related immune genes, risk score, and clinical traits. RESULTS: We selected 8 immune-related genes that can predict the prognosis of LSCC in a COX regression model and plotted the Kaplan-Meier survival curve. The 5-year survival rate of the high-risk group was 16.5% (95% CI: 0.059-0.459), and that of the low-risk group was 72.9% (95% CI: 0.555-0.956). The area under the receiver operating characteristic (ROC) curve was used to confirm the accuracy of the model (AUG = 0.887). After univariate and multivariate regression analysis, the risk score can be used as an independent risk factor for predicting prognosis. The risk score (P = .021) was positively correlated with the clinical Stage classification. CONCLUSION: We screened out 8 immune genes related to prognosis: RBP1, TLR2, AQP9, BTC, EPO, STC2, ZAP70, and PLCG1 to construct risk value models, which can be used to speculate the prognosis of the disease and provide new targets for future immunotherapy.

EGFR and EGFR ligands in serum in healthy women; reference intervals and age dependency.

Background The epidermal growth factor receptor (EGFR) system is involved in cancer pathogenesis and serves as an important target for multiple cancer treatments. EGFR and its ligands epidermal growth factor (EGF), heparin-binding epidermal growth factor (HB-EGF), betacellulin (BTC), amphiregulin (AREG) and transforming growth factor α (TGF-α) have potential applications as prognostic or predictive serological biomarkers in cancer. The aim was to establish EGFR and EGFR ligand reference intervals in healthy women. Methods EGFR and EGFR ligands were measured in serum from 419 healthy women aged 26-78 years. The need for age partitioned reference intervals was evaluated using Lahti's method. EGFR and EGF were analyzed using ELISA assays, whereas HB-EGF, BTC, AREG and TGF-α were analyzed using the highly sensitive automated single molecule array (Simoa) enabling detection below the lower reference limit for all six biomarkers. Results Reference intervals for EGFR and the EGFR ligands were determined as the 2.5th and 97.5th percentiles. All six biomarkers were detectable in all serum samples. For EGFR, EGF, HB-EGF and TGF-α, reference intervals were established for women <55 years and for women >55 years, whilst common reference intervals were established for AREG and BTC including women aged 26-78 years. Conclusions Age specific reference intervals were determined for EGFR, EGF, HB-EGF, BTC, AREG and TGF-α.

Epiregulin is critical for the acinar cell regeneration of the submandibular gland in a mouse duct ligation model.

Acinar cell regeneration from tubular structures has been reported to occur in duct-deligated salivary glands. However, the detailed process of acinar cell regeneration has not been clarified. We have developed a mouse duct ligation model to clarify the mechanisms underlying acinar cell regeneration, and we analyzed the epidermal growth factor receptor (EGFR) and epidermal growth factor (EGF) ligands using the model. We studied these ligands expressions in the course of acinar cell regeneration using immunohistochemistry and RT-PCR methods. In the duct-ligated portion of the submandibular gland (SMG) that underwent atrophy, newly formed acinar cells were observed arising from the tubular structures after the release of the duct obstruction. The constitutive expression of EGFR was observed by immunohistochemistry in both the duct-ligated and duct-deligated animals as well as in normal controls. The EGFR phosphorylation detected on the tubular structures after duct ligation paralleled the acinar cell regeneration. RT-PCR showed an increase in the epiregulin and heparin-binding EGF levels from day 0 to day 3 after the release of the duct obstruction. The EGF level was increased only after day 7. In vitro, cultured cells isolated from ligated SMGs proliferated and produced EGF ligands following the addition of epiregulin to the culture medium. These findings suggest that the tubular structures localized in an atrophic gland are the source of acinar cell regeneration of the salivary gland. The induction of EGF ligands, in particular epiregulin, may play an important role in acinar cell regeneration in this model.