Microbubbles activated by low-frequency ultrasound enhance the anti-tumor effects of curcumin in glioma cells by suppressing the TGF-ß1/Smad/VEGF/NCAM signaling pathway.

This study investigated whether microbubbles activated by low-frequency ultrasound enhanced the anti-tumor effects of curcumin in glioma cells. CCK8 proliferation assay, scratch migration assay, and transwell invasion assay were performed to estimate the proliferation, migration, and invasion rates of the glioma cells in blank control and different treatment groups, respectively. Quantitative RT-PCR (qRT-PCR) analysis was performed to determine the relative expression levels of VEGF and NCAM mRNAs in the various experimental groups. Western blotting was performed to determine the activity status of the TGF-ß1/Smad signaling pathway in various groups of glioma cells by estimating the expression levels of p-SMAD2/3, VEGF, and NCAM proteins. Combined treatment (Cur-Us-MBs) with microbubbles activated by low-frequency ultrasound and curcumin significantly reduced the in vitro proliferation, migration, and invasiveness of glioma cells compared to the control and other treatment groups. Furthermore, Cur-Us-MBs significantly reduced the expression levels of VEGF and NCAM mRNAs and proteins and p-Smad2/3 proteins , including those cells stimulated with rhTGF-ß. These suggested that microbubbles activated by low-frequency ultrasound enhanced the inhibition of TGF-ß1/Smad/VEGF/NCAM signaling pathway by curcumin，and enhanced the antitumor effects of curcumin by significantly reducing in vitro proliferation, migration, and invasiveness of glioma cells through this pathway.

Immune landscape and heterogeneity of cervical squamous cell carcinoma and adenocarcinoma.

Despite the differences in disease outcomes and pathological features between cervical squamous cell carcinoma (CSCC) and adenocarcinoma (ADC), the molecular characteristics in immune heterogeneity of the tumor microenvironment remain unclear. Here, we explored the immune landscape and heterogeneity between CSCC and ADC. Gene expression and clinical characteristics of cervical carcinoma from The Cancer Genome Atlas (TCGA) were downloaded. Differentially expressed genes (DEGs), immune cell infiltration, and pathway enrichment analyses were used to explore the immune landscape and heterogeneity between CSCC and ADC. Furthermore, distinct immune signatures between CSCC and ADC were validated based on clinical samples. In total, 4,132 upregulated DEGs and 2,307 down-regulated DEGs were identified between CSCC and ADC, with enrichments in immune related-pathways in CSCC. In addition, 54 hub DEGs correlated with patients' prognosis and immunocytes infiltration were identified. The CSCC patients had a higher ImmuneScore and more abundant immunocytes infiltration compared to ADC patients, as validated by immunohistochemistry (IHC) and multicolor immunofluorescence (mIF) analyses of collected samples. Furthermore, CSCC displayed higher inhibitory immune checkpoints expression, tumor mutation burden (TMB), and microsatellite instability (MSI) compared to ADC, which indicated CSCC patients were more likely to benefit from immunotherapy. In summary, our results revealed the huge immune heterogeneity between CSCC and ADC, and provided guidance for immunotherapy selection for different pathological types of cervical cancer.

Lipocalin-2 promotes neutrophilic inflammation in nasal polyps and its value as biomarker.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nasal cavity and paranasal sinuses. The role of neutrophils in the pathogenesis of CRSwNP has attracted more attention in recent years, due to its association with more severe disease and reduced steroid responsiveness. Lipocalin-2 (LCN2) has been found to modulate neutrophils infiltration in other neutrophilic inflammation including inflammatory bowel disease, rheumatoid arthritis, and psoriasis. The aim was to evaluate the expression and regulator role of LCN2 in neutrophilic inflammation in CRSwNP, and its role as a potential biomarker predicting non-eosinophilic CRSwNP (neCRSwNP). METHODS: Bioinformatic analysis, immunostainings, real-time PCR and ELISA were used to analyze the expression and location of LCN2 in nasal tissues. The expression of proinflammatory mediators were assessed in nasal tissues and secretions. LCN2 production in human nasal epithelial cells (HNECs) and neutrophils, as well as its role in neutrophilic inflammation was evaluated by in vitro experiments. RESULTS: LCN2 was mainly located in neutrophils and HNECs of nasal polyps. LCN2 expression was also significantly higher in the polyp tissue and nasal secretions from patients with neCRSwNP. The LCN2 levels were positively correlated with type 3 inflammation markers, including G-CSF, IL-8, and IL-17. LCN2 expression could be upregulated by IL-17 A and TNF-α in HNECs, and LCN2 could also promote the expression of IL-8 in dispersed polyp cells and HNECs. CONCLUSIONS: LCN2 could serve as a novel biomarker predicting patients with neCRSwNP, and the increased expression of LCN2 may participate in the pathogenesis of neCRSwNP.

Comparative short-term efficacy of endoscopic sinus surgery and biological therapies in chronic rhinosinusitis with nasal polyps: A network meta-analysis.

BACKGROUND: To compare the safety and efficacy between endoscopic sinus surgery and different biologics in treating chronic rhinosinusitis with nasal polyps in adults by reviewing the existing clinical trials. METHODS: Data extraction and risk of bias assessment were conducted by 2 independent reviewers according to the PRISMA recommendations and any disagreement was resolved by a third investigator. Outcomes were measured through a random-effects model. We searched Embase, Web of Science, MEDLINE, Cochrane, and other relevant sources from its inception to April 30, 2022. We included randomized controlled trials(RCTs) involving endoscopic sinus surgery (ESS) or biologics in treating adult patients with chronic rhinosinusitis with nasal polyps. Studies involving other miscellaneous diseases, non-RCT design, and insufficient participants or follow-up were excluded. RESULTS: In this systematic review, five RCTs and 1748 patients were included. All the biologics, as well as ESS, could significantly improve key nasal outcomes in CRSwNP both at 6 months and 1 year. Dupilumab exhibited better efficacy than ESS in improving SNOT-22 scores at one year. However, ESS showed superiority over three biologics in improving nasal congestion scores (NCS) at two various time points, except for better efficacy of Dupilumab at 1 year. For the loss of smell scores, a greater improvement was observed in the Dupilumab cohort compared with other biologics and even ESS counterparts. Safety analysis showed no significant difference between the ESS cohort and biologic treatment. CONCLUSIONS: In summary, ESS showed comparable improvement in quality of life and symptoms to Omalizumab, Mepolizumab, and Benralizumab. Dupilumab seems to be more effective than ESS in selected items, whereas head-to-head trials and real-world studies are urgent to compare their efficacy. Our findings also showed that biologics could be applied as alternative or adjuvant therapy for uncontrolled severe CRSwNP.

Expression and Prognostic Value of Lgr5 in Patients with Recurrent Nasopharyngeal Carcinoma.

Background: As a cancer stem cells (CSCs) surface marker, Lgr5 plays an important role in the signal transduction of cancer cells and is a potential biomarker for cancer diagnosis and prognosis. However, the expression and prognostic value of Lgr5 in recurrent nasopharyngeal carcinoma (rNPC) remains ambiguous. Materials: We used RNA sequencing to screen differentially expressed mRNAs in eleven specimens of rNPC tissues and five fresh adjacent normal tissue samples and the CSC marker, Lgr5, was identified. The expression level of Lgr5 in rNPC samples was also detected by immunohistochemistry and Western blot assay. The chi-square test was used to analyze the relationship between the clinicopathological variables and the immunostaining of Lgr5. The Log-rank method was used for prognosis analysis. The Cox regression model was used for univariate and multivariate analysis. Results: Significantly elevated expression of Lgr5 in the rNPC tissues was observed compared to the normal tissues using RNA sequencing, Western blot and immunohistochemistry. The expression of Lgr5 was significantly correlated with the T stage (P=0.014). High Lgr5 expression (P=0.007), tumor necrosis (P=0.013) and WHO type II (P=0.043) in rNPC patients exhibited worse overall survival (OS). Lgr5 expression was proved to be an independent risk factor for OS (P=0.035) in multivariate analyses, and had promising predictive value for survival and recurrence in rNPC patients (area under the ROC curve: 0.711 and 0.665, P=0.017 and 0.028, respectively). Conclusion: Lgr5 as a CSC marker is a promising therapeutic target and could be employed to predict the survival prognosis of rNPC patients.

Sinonasal intestinal- and non-intestinal-type adenocarcinoma in China: a retrospective study of 14 cases.

BACKGROUND: In China, reports on the epidemiology of adenocarcinomas of the nasal cavity and paranasal sinuses are limited. AIM: This study aimed to describe the experience of a single institution in China in treating these malignant tumours. MATERIALS AND METHODS: We conducted a retrospective chart review of patients with adenocarcinoma of the nasal cavity and paranasal sinuses admitted between January 2019 and December 2021. Tumour staging was based on the American Joint Committee on Cancer, 8th edition, for sinonasal malignancies. RESULTS: The series included 10 men and 4 women (mean age, 54.5 [range, 14-80] years). Epistaxis and nasal obstruction were the most common clinical manifestations in 10 (71.4%) patients. Ten (71.4%) had stage T4 disease at diagnosis, but no patient had lymph node or distant metastasis. The posterosuperior septum (100.0%) and middle turbinate (92.8%) were the two sites most vulnerable to tumour invasion. All patients underwent endoscopic resection as the initial treatment; one patient died. CONCLUSIONS AND SIGNIFICANCE: In China, these malignancies are related to exposure to certain substances; however, diagnosis can be delayed. Endoscopic resection is a suitable treatment option for adenocarcinomas of the nasal cavity and paranasal sinuses.

The use of vestibular evoked myogenic potentials (VEMP) in the diagnosis of otolithic dysfunction of patients with obstructive sleep apnea: a survey of awareness and recognition of otorhinolaryngology medical staffs.

PURPOSE: To assess awareness and recognition of vestibular function tests in otorhinolaryngology medical staffs, especially the vestibular evoked myogenic potentials (VEMP) testing in patients with obstructive sleep apnea (OSA). METHODS: A survey was delivered via either email or a social media app. The medical staffs of the Chinese Medical Association of Otolaryngology Head and Neck Surgery from various branches were enrolled. Study data were collected and managed with an online data collection tool. RESULTS: A total of 1781 emails and 623 social media messages were sent to 2404 otorhinolaryngology medical staffs. One hundred and fifty-seven of them participated in the survey, including 24 via emails and 133 via the social media app. Regarding the knowledge of VEMP, only 59 (37.6%) of them agreed that OSA could be related to vertigo/dizziness/imbalance and 28 (17.8%) believed that OSA could result in VEMP abnormalities and would factor this in diagnosing the impairment of the vestibular function of OSA patients. A total of 7.6% of the respondents had never heard of the VEMP tests. Responses regarding the minimum age at which VEMP are possible ranged from younger than 6 months to greater than 18 years of age. Beliefs regarding the utility and reliability of VEMP varied, with 'unsure' being the most frequent response. In addition, only 17.8% of otolaryngologists indicated some access to the VEMP test. CONCLUSIONS: Knowledge and beliefs about the role of VEMP in diagnosing otolithic organ dysfunction caused by OSA in otorhinolaryngology vary widely. It is important for otorhinolaryngology medical staffs to learn the latest literatures and updated knowledge through continuing education.

Anatomical studies and early results on endoscopic transoral medial pterygomandibular fold approach to salvage retropharyngeal lymphadenectomy in nasopharyngeal carcinoma.

OBJECTIVE: Retropharyngeal lymphadenectomy is challenging. This study investigated a minimally invasive approach to salvage retropharyngeal lymphadenectomy in patients with nasopharyngeal carcinoma. METHODS: An anatomical study of four fresh cadaveric heads was conducted to demonstrate the relevant details of retropharyngeal lymphadenectomy using the endoscopic transoral medial pterygomandibular fold approach. Six patients with nasopharyngeal cancer with retropharyngeal lymph node recurrence, who underwent retropharyngeal lymphadenectomy with the endoscopic transoral medial pterygomandibular fold technique at the Eye and ENT Hospital of Fudan University from July to December 2021, were included in this study. RESULTS: The anatomical study demonstrated that the endoscopic transoral medial pterygomandibular fold approach offers a short path and minimally invasive approach to the retropharyngeal space. The surgical procedure was well tolerated by all patients, with no significant post-operative complications. CONCLUSION: The endoscopic transoral medial pterygomandibular fold approach is safe and efficient for retropharyngeal lymphadenectomy.

A nomogram for predicting overall survival of patients with sinonasal melanoma: A population-based study.

Objective: Sinonasal melanoma (SMM) is a rare but aggressive malignancy with 5-year overall survival (OS) rates below 40% in published studies. However, the clinicopathological predictors of the prognosis of SMM remain undefined. We aimed to establish a model to predict the survival outcomes of SMM. Methods: We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with SMM between 1975 and 2016. Data on patient demographics, treatment modalities, and survival outcomes were retrieved. Risk factors for OS were evaluated by survival and Cox regression analyses. We also developed and validated a nomogram for OS, and compared its performance with that of conventional staging systems. Results: Overall, 305 SMM patients were included in this population-based study. Multivariate Cox regression showed that primary site, American Joint Committee on Cancer stage, radiotherapy, and surgery were significant risk factors for survival. A nomogram was established using the regression model. The C-indices, areas under the receiver operating characteristic curves, calibration plots, and decision curve analysis demonstrated reliable performance of the nomogram. Conclusion: The nomogram predicting survival outcomes of SMM patients based on clinical information showed good discriminative ability and prognostic accuracy compared with conventional stage classifications. Our nomogram could be used to predict the survival probabilities for SMM patients at different timepoints. Level of Evidence: 2b.

Inhibition of Angiogenesis by MiR-524-5p through Suppression of AKT and ERK Activation by Targeting CXCR7 in Colon Cancer Cells.

Increasing evidence shows that alterations in microRNA (miRNA) expression are involved in the occurrence and development of various malignant tumors, including colon cancer. MiRNA-524-5p has been reported to have anticancer activity in colon cancer. This study explored the influence of the miRNA-524-5p/CXCR7 axis on angiogenesis using colon cancer cells and further studied the mechanisms involved. We found that changing the expression of miRNA-524-5p can affect colonic proliferation, migration, and angiogenesis. Furthermore, angiogenesis induced by miRNA-524-5p overexpression was reversed by overexpression of CXCR7 in HT-29 cells, while the opposite was observed in Caco-2 cells. Furthermore, miRNA-524-5p inhibited the activation of AKT and ERK signaling by targeting CXCR7. Overall, our results indicated that the miRNA-524-5p/CXCR7 axis regulated angiogenesis in colon cancer cells through the AKT and ERK pathways.

Low-intensity ultrasound: A novel technique for adjuvant treatment of gliomas.

Glioma is the most common primary malignant tumor of the central nervous system. Although surgical treatment combined with radiotherapy, chemotherapy, and immunotherapy are commonly used for glioma treatment, the prognosis of glioma is still unsatisfactory. The poor effect of glioma treatment could be due to the blocking effect of blood-brain barrier (BBB) on most drugs and the multidrug resistance in tumor cells. In recent years, preclinical trials have shown that low-intensity ultrasound (LIUS) can reversibly open the BBB, inhibit the proliferation of tumor cells, and improve the delivery of drugs to brain tissue. This technology has also recently been used in clinical trials, and achieved encouraging preliminary results. In this review, the existing research results, the effect of LIUS on the adjuvant therapy of glioma under safe conditions, and the physical and biological mechanisms have been discussed. This review aims to show the potential and prospect of LIUS technique in the clinical treatment of glioma.

[The application of submental flap in the nasopharyngectomy for nasopharyngeal carcinoma].

Objective:To explore the anatomy and clinical application of submental flap in the nasopharyngectomy for nasopharyngeal carcinoma. Methods:The anatomical study of the submental flap was carried out on 5 cadavers, focusing on exploring the channel of the submental flap transposition to the nasopharyngeal skull base area, and analyzing the nasopharyngeal skull base area covered by the submental flap. A retrospective analysis of 4 patients with submental flap repairment after nasopharyngectomy was performed, and the surgical methods and techniques of submental flap to repair nasopharyngeal nasal skull base defect were introduced in detail. Rusults: It showed that the submental flap could be transposed into the nasopharyngeal skull base through the posteromedial of the mandible-posterior pterygoid muscle-parapharyngeal space channel, and could cover the paraclival internal carotid artery. Clinical practice showed that the submental flap was successfully used to repair the nasopharyngeal skull base defect in 4 patients, and the submental flap grew well in the follow-up. Conclusion:The submental flap is suitable for the repair of the nasopharyngeal skull base defect after nasopharyngeal carcinoma surgery, and it is worthy of clinical promotion.

Transinfratemporal Fossa Transposition of the Temporalis Muscle Flap for Skull Base Reconstruction after Endoscopic Expanded Nasopharyngectomy: Anatomical Study and Clinical Application.

Objective Temporalis muscle flap (TMF) is widely used in traditional skull base surgery, but its application in endoscopic skull base surgery remains rarely reported. We aimed to investigate the surgical anatomy and clinical application of TMF for reconstruction of skull base defects after expanded endoscopic nasopharyngectomy. Methods Nine fresh cadaver heads (18 sides) were used for endoscopic dissection at the University of Pittsburgh School of Medicine in the United States. TMF was harvested using a traditional open approach and then transposed into the maxillary sinus and nasal cavity through the infratemporal fossa using an endoscopic transnasal transmaxillary approach. TMF length was then measured. Moreover, TMF was used for the reconstruction of skull base defects of six patients with recurrent nasopharyngeal carcinoma after expanded endoscopic nasopharyngectomy. Results The length of TMF harvested from the temporal line to the tip of the coronoid process of the mandible was 11.8 ± 0.9 cm. The widest part of the flap was 9.0 ± 0.4 cm. When TMF was dislocated from the coronoid process of the mandible, approximately another 2 cm of reach could be obtained. When the superficial layer of the temporalis muscle was split from the deep layer, the pedicle length could be extended 1.9 ± 0.2 cm. TMF could cover skull base defects in the anterior skull base, sellar, and clivus regions. Conclusion TMF can be used to reconstruct skull base defects after endoscopic expanded nasopharyngectomy and can effectively prevent the occurrence of serious complications in patients with recurrent nasopharyngeal carcinoma.

Identification and Validation of Immune Infiltration Phenotypes in Laryngeal Squamous Cell Carcinoma by Integrative Multi-Omics Analysis.

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the world's most common head and neck cancer. However, the immune infiltration phenotypes of LSCC have not been well investigated. Methods: The multi-omics data of LSCC were obtained from the TCGA (n=111) and GEO (n=57) datasets. The infiltrations of the 24 immune cell populations were calculated using the GSVA method. Then LSCC samples with different immune cell infiltrating patterns were clustered, and the multi-omics differences were investigated. Results: Patients were clustered into the high-infiltration and low-infiltration groups. The infiltration scores of most immune cells were higher in the high-infiltration group. Patients with high-infiltration phenotype have high N and TNM stages but better survival, as well as less mutated COL11A1 and MUC17. Common targets of immunotherapies such as PD1, PDL1, LAG3, and CTLA4 were significantly up-regulated in the high-infiltration group. The differentially expressed genes were mainly enriched in several immune-related GOs and KEGG pathways. Based on the genes, miRNAs, and lncRNAs differentially expressed in both the TCGA and GEO cohorts, we built a ceRNA network, in which BTN3A1, CCR1, miR-149-5p, and so on, located at the center. A predictive model was also constructed to calculate a patient's immune infiltration phenotype using 16 genes' expression values, showing excellent accuracy and specificity in the TCGA and GEO cohorts. Conclusions: In this study, the immune infiltration phenotypes of LSCC and the corresponding multi-omics differences were explored. Our model might be valuable to predicting immunotherapy's outcome.

[Endoscopic transoral retropharyngeal lymphadenectomy].

Objective:The aim of this study is to explore the anatomy and surgical approach of retropharyngeal lymphadenectomy via endoscopic transoral approach. Methods:The retropharyngeal spaces were studied with three fresh frozen cadaver head （6 sides） in the anatomical laboratory of Eye, Ear, Nose and Throat Hospital of Fudan University through endoscopic transoral approach. The superior pharyngeal constrictor muscle, medial pterygoid muscle, tendon of tensor veli palatini muscle, fat of prestyloid space, ascending palatine artery and its branches, styloglossus, stylopharyngeus, stylohyoideus, external carotid artery, levator veli palatini, carotid sheath, ascending pharyngeal artery and longus capitis muscle were revealed in order. The above-mentioned structures were photographed with a 0° Karl Storz nasal endoscope and adjacent relationships were recorded. A case of metastatic retropharyngeal lymphadenopathy was reviewed and the surgical methods and techniques of retropharyngeal lymphadenectomy via endoscopic transoral approach were introduced in detail. Results:The retropharyngeal space and related anatomical structures were exposed through endoscopic transoral approach in all specimens. The styloglossus, stylopharyngius and levator veli palatini are the markers of locating the internal carotid artery. The superior pharyngeal constrictor muscle, medial pterygoid muscle, styloid muscle group, longus capitis muscle and carotid sheath are the markers that can be used to locate the retropharyngeal lymph nodes. Ascending palatine artery, ascending pharyngeal artery and internal carotid artery are the main arteries involved in retropharyngeal lymphadenectomy via endoscopic transoral approach. Conclusion:Endoscopic transoral approach is a new surgical technique to perform retropharyngeal lymphadenectomy safely and completely.

Serum and glucocorticoid-regulated kinase 1 regulates transforming growth factor ß1-connective tissue growth factor pathway in chronic rhinosinusitis.

PURPOSE: Serum/glucocorticoid-regulated kinase 1 (SGK1) has been identified as a crucial regulator in fibrotic disorders. Herein, we explored SGK1 role in tissue remodeling of chronic rhinosinusitis (CRS). METHODS: Lentivirus was employed to generate an SGK1-overexpressing human bronchial epithelial cell (16HBE) line. To screen SGK1 downstream genes, RNA sequencing was performed on SGK1-overexpressing and control cell lines. To determine protein and gene expression levels, immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction were employed. Correlation analysis was performed using mRNA expression levels of SGK1, transforming growth factor ß1 (TGF-ß1), and connective tissue growth factor (CTGF) derived from CRS mucosal tissue and GEO database. Gene set enrichment analysis was conducted using gene sets from Molecular Signatures Database. The severity of symptoms in CRS patients was assessed using the 22-Item Sinonasal Outcome Test. RESULTS: SGK1 overexpression significantly increased the expression of connective tissue growth factor (CTGF) in 16HBE cells (P < 0.01). Consistently, CTGF protein level was considerably greater in mucosal tissue of CRS without nasal polyps (CRSsNP) than in CRS with nasal polyps (CRSwNP) (P < 0.05) or in control subjects (P < 0.01). TGF-ß1 protein level was higher in mucosal tissue of CRSsNP patients than in CRSwNP patients (P < 0.001) or in the control group (P < 0.01). mRNA levels of SGK1 and CTGF (P < 0.05, r = 0.668; P = 0.001, r = 0.630), TGF-ß1 and CTGF (P < 0.05, r = 0.560; P < 0.05, r = 0.420), as well as SGK1 and TGF-ß1(P < 0.05, r = 0.612; P < 0.05, r = 0.524) were significantly correlated in CRS mucosal tissue and GSE36830 dataset, respectively. TGF-ß1-induced upregulated genes were significantly enriched in SGK1 overexpression group. In vitro assays, TGF-ß1 promoted SGK1 and CTGF expression in a concentration- and time-dependent manner. Administrating an SGK1 inhibitor, GSK650394, significantly inhibited TGF-ß1-induced CTGF expression in 16HBE and dispersed primary nasal polyp cells. CONCLUSIONS: TGF-ß1 stimulation significantly increases SGK1 and CTGF expression. By regulating TGF-ß1-CTGF pathway, SGK1 may participate in tissue remodeling in the pathological mechanism of CRS.

Identification of Heat Shock Protein 90 as a Recurrence Related Marker in Juvenile Nasopharyngeal Angiofibroma.

BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) is a highly recurrent tumor after curative surgery. OBJECTIVE: The purpose of this study was to evaluate heat shock protein 90 (HSP90) expression in JNA and its association with tumor recurrence. METHODS: Immunohistochemistry was performed to assess HSP90 expression using tissue microarrays containing 70 JNA patients and 10 control subjects. The associations of HSP90 expression with clinicopathological features and tumor recurrence were analyzed. RESULTS: Immunohistochemistry revealed high HSP90 expression in JNA compared with normal middle turbinate samples. High expression of HSP90, which correlated with MVD (P = .001), ER-α (P = .001), VEGF (P < .001) and JNA recurrence (P = .009), was an independent prognostic factor of time to recurrence (P = .017). The combination of HSP90 and ER-α had a better power to predict disease recurrence than other clinicopathological features (P = .008). CONCLUSIONS: HSP90 may be an independent prognostic marker in JNA patients administered surgical treatment. Combination of HSP90 and ER-α expression may be the best predictor of tumor recurrence among all clinicopathological factors.

Interaction Between Serum/Glucocorticoid-Regulated Kinase 1 and Interleukin-6 in Chronic Rhinosinusitis.

PURPOSE: Serum/glucocorticoid-regulated kinase 1 (SGK1) has recently emerged as a critical regulator of inflammatory diseases. In this study, we examined SGK1 expression and its possible pathogenic roles in chronic rhinosinusitis (CRS). METHODS: Immunohistochemistry, western blotting, Bio-Plex assay, enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction were performed to assess protein and gene expression levels. The mRNA expression levels of SGK1 and interleukin-6 (IL-6) were extracted from a CRS database to perform correlation analysis. Stable cell lines with SGK1 overexpression (16HBE) and knockdown (A549) were constructed to investigate the interaction between SGK1 and IL-6 in vitro. RESULTS: SGK1 exhibited strong cytoplasmic and nuclear staining in the epithelial layers and the lamina propria of nasal polyps (NPs) and in the mucosal tissues of CRS without nasal polyps (CRSsNP). The mRNA and protein expression levels of SGK1 and IL-6 were significantly increased in NPs and CRSsNP tissues, compared to control tissues. SGK1 phosphorylation was significantly greater in NPs than in CRSsNP tissues (P < 0.01). The mRNA levels of SGK1 and IL-6 were significantly correlated (P < 0.001, r = 0.649). Exposure to IL-6 significantly increased SGK1 expression in cultured dispersed NP cells, 16HBE cells, and A549 cells. IL-6 expression was significantly down-regulated in SGK1-overexpressing 16HBE cells (P < 0.01) and significantly up-regulated in SGK1-knockdown A549 cells (P < 0.05). Administration of GSK650394, a SGK1 inhibitor, significantly increased IL-6 self-induced mRNA expression in cultured dispersed NP cells and 16HBE cells. CONCLUSIONS: The interaction between SGK1 and IL-6 may play an anti-inflammatory role in IL-6-induced inflammation in the pathogenesis of CRS.

Identification of a Costimulatory Molecule Gene Signature to Predict Survival and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide. Checkpoint blockade immunotherapy has made tremendous progress in the treatment of a variety of cancers in recent years. Costimulatory molecules constitute the foundation of cancer immunotherapies and are deemed to be promising targets for cancer treatment. This study attempted to evaluate the potential value of costimulatory molecule genes (CMGs) in HNSCC. MATERIALS AND METHODS: Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, we identified the prognostic value of CMGs in HNSCC. Subsequently, CMGs-based signature (CMS) to predict overall survival of HNSCC patients was established and validated. The differences of downstream pathways, clinical outcomes, immune cell infiltration, and predictive immunotherapy responses between different CMS subgroups were investigated via bioinformatic algorithms. We also explored the biological functions of TNFRSF12A, one risk factor of CMS, by in vitro experiments. RESULTS: Among CMGs, 22 genes were related to prognosis based on clinical survival time in HNSCC. Nine prognosis-related CMGs were selected to establish CMS. CMS was an independent risk factor and could indicate the survival of HNSCC patients, the component of tumor-infiltrating lymphocytes, and the immunotherapy response rate. Functional enrichment analysis confirmed that CMS might involve immune-relevant processes. Additionally, TNFRSF12A was related to poor prognosis and enhanced malignant phenotype of HNSCC. CONCLUSION: Collectively, CMS could accurately indicate prognosis, evaluate the tumor immune microenvironment, and predict possible immunotherapy outcomes for HNSCC patients.

Identification of key pseudogenes in nasopharyngeal carcinoma based on RNA-Seq analysis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant head and neck tumor, and more than 70% of new cases are in East and Southeast Asia. However, association between NPC and pseudogenes playing important roles in genesis of multiple tumor types is still not clear and needs to be investigated. METHODS: Using RNA-Sequencing (RNA-seq) technology, we analyzed pseudogene expression in 13 primary NPC and 6 recurrent NPC samples as well as their paracancerous counterparts. Quantitative PCR was used to validate the differentially expressed pseudogenes. RESULTS: We found 251 differentially expressed pseudogenes including 73 up-regulated and 178 down-regulated ones between primary NPC and paracancerous tissues. Enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were conducted to filter out the key pseudogenes. We reported that pseudogenes from cytochrome P450 (CYP) family, such as CYP2F2P, CYP2G1P, CYP4F24P, CYP2B7P and CYP2G2P were significantly down-regulated in NPC compared to paracancerous tissues, while IGHV1OR15-2, IGHV3-11, FCGR1CP and IGHV3-69-1 belonging to Fc gamma receptors were significantly up-regulated. CYP2B7P, CYP2F2P and CYP4F26P were enriched in arachidonic acid metabolism pathway. The qRT-PCR analysis validated the lower expression of pseudogenes CYP2F2P and CYP2B7P in NPC tissues and cell lines compared to paracancerous tissues and normal human nasopharyngeal epithelial cell line. CYP2B7P overexpression weakened migratory and invasive capacity of NPC cell line. Moreover, the expression pattern of those pseudogenes in recurrent NPC tissues was different from the primary NPC. CONCLUSION: This study suggested the role of pseudogenes in tumorigenesis and progression, potentially functioning as therapeutic targets to NPC.